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Vimalanathan B, Thiyagarajan D, Mary RN, Sachidanandam M, Ignacimuthu S, Gnanasampanthapandian D, Rajasingh J, Palaniyandi K. Composites of Reduced Graphene Oxide Based on Silver Nanoparticles and Their Effect on Breast Cancer Stem Cells. Bioengineering (Basel) 2025; 12:508. [PMID: 40428127 DOI: 10.3390/bioengineering12050508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 05/05/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
Graphene and its related nanocomposites have garnered significant interest due to their distinct physiochemical and biological properties. In this study, reduced graphene oxide-silver hybrid nanostructures were synthesized for applications in biomedical nanotechnology, particularly in targeting cancer stem cells (CSCs). A range of analytical techniques, such as X-ray diffraction (XRD), Raman spectroscopy, Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and UV-visible absorption spectroscopy (UV-VIS), were employed to characterize graphene oxide (GO), reduced graphene oxide (rGO)-silver nanoparticles (AgNPs), and their composite structures. The GO-rGO-AgNPs exhibited potent anticancer properties as evidenced by cell culture assays, spheroid formation assay, and quantitative RT-PCR analysis. Treatment of breast cancer cells (MCF-7) with GO, rGO, and AgNPs significantly reduced cell proliferation and mammosphere formation. Furthermore, these treatments downregulated the expression of marker genes associated with CSCs in MCF-7 cells. Among the tested materials, rGO-AgNP, sodium citrate-mediated GO-AgNP, and rGO-AgNP nanocomposites demonstrated superior inhibitory effects on cell survival compared to GO alone. These findings suggest that these nanocomposites hold promise as effective and non-toxic therapeutic agents for targeting cancer cells and CSCs, thereby offering a novel approach to cancer treatment.
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Affiliation(s)
- Babu Vimalanathan
- Crystal Growth Centre, Anna University, Chennai 600025, Tamil Nadu, India
| | - Devasena Thiyagarajan
- Centre for Nanoscience and Nanotechnology, Anna University, Chennai 600025, Tamil Nadu, India
| | - Ruby Nirmala Mary
- Department of Biotechnology, Periyar Maniammai Institute of Science and Technology, Thanjavur 613403, Tamil Nadu, India
| | - Magesh Sachidanandam
- Department of Virology, King Institute of Preventive Medicine and Research, Chennai 600032, Tamil Nadu, India
| | - Savarimuthu Ignacimuthu
- Xavier Research Foundation, St Xavier's College, Palayamkottai, Tirunelveli 627002, Tamil Nadu, India
| | - Dhanavathy Gnanasampanthapandian
- Cancer Science Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Chennai 603203, Tamil Nadu, India
| | - Johnson Rajasingh
- Department of Bioscience Research & Medicine-Cardiology, The University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Kanagaraj Palaniyandi
- Cancer Science Laboratory, Department of Biotechnology, SRM Institute of Science and Technology, Chennai 603203, Tamil Nadu, India
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Rahimkhoei V, Akbari A, Jassim AY, Hussein UAR, Salavati-Niasari M. Recent advances in targeting cancer stem cells by using nanomaterials. Int J Pharm 2025; 673:125381. [PMID: 39988213 DOI: 10.1016/j.ijpharm.2025.125381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 02/12/2025] [Accepted: 02/19/2025] [Indexed: 02/25/2025]
Abstract
Cancer stem cells (CSCs) are a special group of cells that start, regenerate, and maintain the growth of tumors. Cancer stem cells (CSCs) contribute to the dissemination of tumors, their recurrence following treatment, and the mechanisms by which cancers develop resistance to therapies. CSCs reside in a unique microenvironment influenced by a variety of factors from their immediate surroundings. These factors include low oxygen levels, too much new blood vessel growth, a shift in how cells use energy from breathing oxygen to breaking down glucose, and an increase in certain markers and signals related to stem cells that help remove drugs from the body. Antibodies and special molecules that focus on the unique features keeping the environment stable are used to deliver cancer treatments to CSCs. As a result, nanoparticles are extremely effective in delivering drugs that combat cancer directly to cancer stem cells. Right now, stem cell nanotechnology is a new and interesting area of study. Some experiments on how stem cells interact with tiny structures or materials have shown good results. The importance of tiny structures and materials in creating treatments using stem cells for diseases and injuries has been clearly understood. The way nanomaterials are built and their characteristics influence how stem cells grow and change. This area of study is a new and exciting field where material science meets medicine. This review talks about the biology of CSCs and new ways to create nanoparticles (NPs) that can deliver cancer drugs specifically to these CSCs. This review talks about the creation of different types of tiny particles, including synthetic and natural polymer particles, lipid particles, inorganic particles, protein particles that can assemble themselves, combined antibody-drug particles, and small bubbles called nanovesicles, all aimed at targeting cancer stem cells. This paper talks about recent progress and opinions on using nanotechnology in stem cell research and therapy. It also covers how nanoparticles can help track, control, and improve the retention of stem cells.
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Affiliation(s)
- Vahid Rahimkhoei
- Institute of Nano Science and Nano Technology, University of Kashan, Kashan 87317-51167, Islamic Republic of Iran
| | - Ali Akbari
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Amar Yasser Jassim
- Department of Marine Vertebrate, Marine Science Center, University of Basrah, Iraq
| | | | - Masoud Salavati-Niasari
- Institute of Nano Science and Nano Technology, University of Kashan, Kashan 87317-51167, Islamic Republic of Iran.
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3
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Mitranovici MI, Caravia LG, Moraru L, Pușcașiu L. Targeting Cancer Stemness Using Nanotechnology in a Holistic Approach: A Narrative Review. Pharmaceutics 2025; 17:277. [PMID: 40142941 PMCID: PMC11945010 DOI: 10.3390/pharmaceutics17030277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 01/20/2025] [Accepted: 02/18/2025] [Indexed: 03/28/2025] Open
Abstract
Increasing evidence shows that a very small population of cancer stem cells (CSCs) is responsible for cancer recurrence, drug resistance, and metastasis. CSCs usually reside in hypoxic tumor regions and are characterized by high tumorigenicity. Their inaccessible nature allows them to avoid the effects of conventional treatments such as chemotherapy, radiotherapy, and surgery. In addition, conventional chemo- and radiotherapy is potentially toxic and could help CSCs to spread and survive. New therapeutic targets against CSCs are sought, including different signaling pathways and distinct cell surface markers. Recent advances in nanotechnology have provided hope for the development of new therapeutic avenues to eradicate CSCs. In this review, we present newly discovered nanoparticles that can be co-loaded with an apoptosis-inducing agent or differentiation-inducing agent, with high stability, cellular penetration, and drug release. We also summarize the molecular characteristics of CSCs and the signaling pathways responsible for their survival and maintenance. Controlled drug release targeting CSCs aims to reduce stemness-related drug resistance, suppress tumor growth, and prevent tumor relapse and metastases.
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Affiliation(s)
- Melinda-Ildiko Mitranovici
- Department of Anatomy, Faculty of Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania;
| | - Laura Georgiana Caravia
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Liviu Moraru
- Department of Anatomy, Faculty of Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania;
| | - Lucian Pușcașiu
- Department of Anatomy, Faculty of Medicine, “George Emil Palade” University of Medicine, Pharmacy, Science and Technology, 540142 Targu Mures, Romania;
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Hajipour Keyvani A, Mohammadnejad P, Pazoki-Toroudi H, Perez Gilabert I, Chu T, Manshian BB, Soenen SJ, Sohrabi B. Advancements in Cancer Treatment: Harnessing the Synergistic Potential of Graphene-Based Nanomaterials in Combination Therapy. ACS APPLIED MATERIALS & INTERFACES 2025; 17:2756-2790. [PMID: 39745785 DOI: 10.1021/acsami.4c15536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2025]
Abstract
Combination therapy, which involves using multiple therapeutic modalities simultaneously or sequentially, has become a cornerstone of modern cancer treatment. Graphene-based nanomaterials (GBNs) have emerged as versatile platforms for drug delivery, gene therapy, and photothermal therapy. These materials enable a synergistic approach, improving the efficacy of treatments while reducing side effects. This review explores the roles of graphene, graphene oxide (GO), and graphene quantum dots (GQDs) in combination therapies and highlights their potential to enhance immunotherapy and targeted cancer therapies. The large surface area and high drug-loading capacity of graphene facilitate the codelivery of multiple therapeutic agents, promoting targeted and sustained release. GQDs, with their unique optical properties, offer real-time imaging capabilities, adding another layer of precision to treatment. However, challenges such as biocompatibility, long-term toxicity, and scalability need to be addressed to ensure clinical safety. Preclinical studies show promising results for GBNs, suggesting their potential to revolutionize cancer treatment through innovative combination therapies.
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Affiliation(s)
- Armin Hajipour Keyvani
- Surface Chemistry Research Laboratory, Faculty of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
| | - Parizad Mohammadnejad
- Surface Chemistry Research Laboratory, Faculty of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
| | - Hamidreza Pazoki-Toroudi
- Physiology Research Center, Faculty of Medicine, Iran University of Medical Sciences, Tehran 14496-14535, Iran
| | - Irati Perez Gilabert
- NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Rellis Research Group, Gaston Geenslaan 3 - Box 901, 3001 Leuven, Belgium
| | - Tianjiao Chu
- NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Rellis Research Group, Gaston Geenslaan 3 - Box 901, 3001 Leuven, Belgium
| | - Bella B Manshian
- Translational Cell and Tissue Research Unit, Department of Imaging and Pathology, KU Leuven, RK-Herestraat 49 - Box 505,3000 Leuven, Belgium
| | - Stefaan J Soenen
- NanoHealth and Optical Imaging Group, Department of Imaging and Pathology, KU Leuven, Rellis Research Group, Gaston Geenslaan 3 - Box 901, 3001 Leuven, Belgium
- Leuven Cancer Institute, Faculty of Medicine, KU Leuven, Rellis Research Group, Gaston Geenslaan 3 - Box 901, 3001 Leuven, Belgium
| | - Beheshteh Sohrabi
- Surface Chemistry Research Laboratory, Faculty of Chemistry, Iran University of Science and Technology, Tehran 16846-13114, Iran
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Hao C, Chen P, Setrerrahmane S, Xu H. A peptide-salinomycin conjugate with a bystander effect reduces the stemness characteristics of ovarian cancer cells and enhances drug sensitivity. Eur J Med Chem 2024; 276:116701. [PMID: 39067438 DOI: 10.1016/j.ejmech.2024.116701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 07/07/2024] [Accepted: 07/18/2024] [Indexed: 07/30/2024]
Abstract
Salinomycin (Sal) has attracted considerable attention in the field of tumor treatment, especially for its inhibitory effect on cancer stem cells (CSCs) and drug-resistant tumor cells. However, its solubility and targeting specificity pose significant challenges to its pharmaceutical development. Sal-A6, a novel peptide-drug conjugate (PDC), was formed by linking the peptide A6 targeting the CSC marker CD44 with Sal using a specific linker. This conjugation markedly enhances the physicochemical properties of Sal and compared to Sal, Sal-A6 demonstrated a significantly increased activity against ovarian cancer. Furthermore, Sal-A6, employing a disulfide bond as a linker, exhibited bystander killing effect. Moreover, it induces substantial cytotoxic effect on both cancer stem cells and drug-resistant cells in addition to enhance chemosensitivity of resistant ovarian cancer cells. In summary, the results indicated that Sal-A6, a novel PDC derived from Sal, has potential therapeutic applications in the treatment of ovarian cancer and drug-resistant patients. Additionally, this discovery offers insights for developing PDC-type drugs using Sal as a foundation.
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Affiliation(s)
- Chaowei Hao
- The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing 210009, P.R. China; State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | - Peng Chen
- The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing 210009, P.R. China; State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China
| | | | - Hanmei Xu
- The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, Jiangsu Province, China Pharmaceutical University, Nanjing 210009, P.R. China; State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, 210009, China.
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Andreani T, Cheng R, Elbadri K, Ferro C, Menezes T, Dos Santos MR, Pereira CM, Santos HA. Natural compounds-based nanomedicines for cancer treatment: Future directions and challenges. Drug Deliv Transl Res 2024; 14:2845-2916. [PMID: 39003425 PMCID: PMC11385056 DOI: 10.1007/s13346-024-01649-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2024] [Indexed: 07/15/2024]
Abstract
Several efforts have been extensively accomplished for the amelioration of the cancer treatments using different types of new drugs and less invasives therapies in comparison with the traditional therapeutic modalities, which are widely associated with numerous drawbacks, such as drug resistance, non-selectivity and high costs, restraining their clinical response. The application of natural compounds for the prevention and treatment of different cancer cells has attracted significant attention from the pharmaceuticals and scientific communities over the past decades. Although the use of nanotechnology in cancer therapy is still in the preliminary stages, the application of nanotherapeutics has demonstrated to decrease the various limitations related to the use of natural compounds, such as physical/chemical instability, poor aqueous solubility, and low bioavailability. Despite the nanotechnology has emerged as a promise to improve the bioavailability of the natural compounds, there are still limited clinical trials performed for their application with various challenges required for the pre-clinical and clinical trials, such as production at an industrial level, assurance of nanotherapeutics long-term stability, physiological barriers and safety and regulatory issues. This review highlights the most recent advances in the nanocarriers for natural compounds secreted from plants, bacteria, fungi, and marine organisms, as well as their role on cell signaling pathways for anticancer treatments. Additionally, the clinical status and the main challenges regarding the natural compounds loaded in nanocarriers for clinical applications were also discussed.
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Affiliation(s)
- Tatiana Andreani
- Chemistry Research Centre (CIQUP) and Institute of Molecular Sciences (IMS), Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua Do Campo Alegre s/n, 4169-007, Porto, Portugal
- GreenUPorto-Sustainable Agrifood Production Research Centre & Inov4Agro, Department of Biology, Faculty of Sciences of University of Porto, Rua Campo Alegre s/n, 4169-007, Porto, Portugal
| | - Ruoyu Cheng
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland
- Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute Groningen (PRECISION), University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands
| | - Khalil Elbadri
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland
| | - Claudio Ferro
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland
- Research Institute for Medicines, iMed.Ulisboa, Faculty of Pharmacy, Universidade de Lisboa, 1649-003, Lisbon, Portugal
| | - Thacilla Menezes
- Chemistry Research Centre (CIQUP) and Institute of Molecular Sciences (IMS), Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua Do Campo Alegre s/n, 4169-007, Porto, Portugal
| | - Mayara R Dos Santos
- Chemistry Research Centre (CIQUP) and Institute of Molecular Sciences (IMS), Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua Do Campo Alegre s/n, 4169-007, Porto, Portugal
| | - Carlos M Pereira
- Chemistry Research Centre (CIQUP) and Institute of Molecular Sciences (IMS), Department of Chemistry and Biochemistry, Faculty of Sciences of University of Porto, Rua Do Campo Alegre s/n, 4169-007, Porto, Portugal
| | - Hélder A Santos
- Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.
- Department of Biomaterials and Biomedical Technology, The Personalized Medicine Research Institute Groningen (PRECISION), University Medical Center Groningen, University of Groningen, 9713 AV, Groningen, The Netherlands.
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Zhan H, Lv Y, Shen R, Li C, Li M, Li Y. Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner. Mol Pharm 2024; 21:1450-1465. [PMID: 38335466 DOI: 10.1021/acs.molpharmaceut.3c01100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/12/2024]
Abstract
The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.
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Affiliation(s)
- Honglei Zhan
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, Liaoning Province 116034, P. R. China
| | - Yulong Lv
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, Liaoning Province 116034, P. R. China
| | - Ruiyu Shen
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, Liaoning Province 116034, P. R. China
| | - Chaoyue Li
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, Liaoning Province 116034, P. R. China
| | - Miao Li
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, Liaoning Province 116034, P. R. China
| | - Yahong Li
- Research Institute of Photonics, Dalian Polytechnic University, Dalian, Liaoning Province 116034, P. R. China
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Zhan H, Ding S, Shen R, Lv Y, Tian X, Liu G, Li C, Wang J. A Green Synthesis of Au-Ag Alloy Nanoparticles using Polydopamine Chemistry: Evaluation of their Anticancer Potency Towards Both MCF-7 Cells and their Cancer Stem Cells Subgroup. Anticancer Agents Med Chem 2024; 24:969-981. [PMID: 38616743 DOI: 10.2174/0118715206296123240331050206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Revised: 03/02/2024] [Accepted: 03/13/2024] [Indexed: 04/16/2024]
Abstract
BACKGROUND Limited chemotherapy efficacy and cancer stem cells (CSCs)-induced therapeutic resistance are major difficulties for tumour treatment. Adopting more efficient therapies to eliminate bulk-sensitive cancer cells and resistant CSCs is urgently needed. METHODS Based on the potential and functional complementarity of gold and silver nanoparticles (AuNPs or AgNPs) on tumour treatment, bimetallic NPs (alloy) have been synthesized to obtain improved or even newly emerging bioactivity from a combination effect. This study reported a facile, green and economical preparation of Au-Ag alloy NPs using biocompatible polydopamine (PDA) as a reductant, capping, stabilizing and hydrophilic agent. RESULTS These alloy NPs were quasi-spherical with rough surfaces and recorded in diameters of 80 nm. In addition, these alloy NPs showed good water dispersity, stability and photothermal effect. Compared with monometallic counterparts, these alloy NPs demonstrated a dramatically enhanced cytotoxic/pro-apoptotic/necrotic effect towards bulk-sensitive MCF-7 and MDA-MB-231 cells. The underlying mechanism regarding the apoptotic action was associated with a mitochondria-mediated pathway, as evidenced by Au3+/Ag+ mediated Mitochondria damage, ROS generation, DNA fragmentation and upregulation of certain apoptotic-related genes (Bax, P53 and Caspase 3). Attractively, these Au-Ag alloy NPs showed a remarkably improved inhibitory effect on the mammosphere formation capacity of MCF-7 CSCs. CONCLUSION All the positive results were attributed to incorporated properties from Au, Ag and PDA, the combination effect of chemotherapy and photothermal therapy and the nano-scaled structure of Au-Ag alloy NPs. In addition, the high biocompatibility of Au-Ag alloy NPs supported them as a good candidate in cancer therapy.
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Affiliation(s)
- Honglei Zhan
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Shiyu Ding
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Ruiyu Shen
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Yulong Lv
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Xinran Tian
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Guie Liu
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Chaoyue Li
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
| | - Jihui Wang
- Department of Biopharmacy, School of Bioengineering, Dalian Polytechnic University, Dalian, 116034, Liaoning Province, P.R. China
- School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan, 523808, Guangzhou Province, P.R. China
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9
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Bekasova O. Properties and potential applications of bioconjugates of R-phycoerythrin with Ag° or CdS nanoparticle synthesized in its tunnel cavity: A review. Int J Biol Macromol 2024; 255:128181. [PMID: 37977463 DOI: 10.1016/j.ijbiomac.2023.128181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 11/09/2023] [Accepted: 11/14/2023] [Indexed: 11/19/2023]
Abstract
Green synthesis is a promising method for the preparation of nanoparticles (NPs) due to its simplicity, low cost, low toxicity, and environmental friendliness. Biosynthesized NPs exhibit multifunctional activity, good biocompatibility, and higher anticancer and antibacterial activity compared to chemically synthesized NPs. R-phycoerythrin, a photosynthetic light-harvesting pigment of protein nature (M.w. 290 kDa), is an attractive platform for the synthesis of small sizes NPs due to its structural features, non-toxicity, water solubility. Photosensitive bioconjugates of R-phycoerythrin with NPs were prepared by synthesizing Ag° and CdS NPs in tunnel cavities of R-phycoerythrin (3.5 × 6.0 nm) isolated from the red seaweed Callithamnion rubosum. The review is devoted to the physical processes and chemical reactions that occur in the native protein macromolecule of a complex structure during the synthesis of a NP in its cavity. The influence of Ago and CdS NPs on the electronic processes caused by the absorption of photons, leading to reversible and irreversible changes in R-phycoerythrin has been analyzed. Properties of R-phycoerythrin bioconjugates Ag° and CdS with NPs combined with the literature data suggest potential applications of Ag°⋅PE and CdS⋅PE bioconjugates for cancer diagnosis, treatment, and monitoring as well as for realizing theranostic strategy in the future. The use of these bioconjugates in anticancer therapy may have synergistic effects since both R-phycoerythrin and NPs induce cancer cell death.
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Affiliation(s)
- Olga Bekasova
- Bach Institute of Biochemistry, Federal Research Centre "Fundamentals of Biotechnology", Russian Academy of Sciences, Leninskiy pr. 33, Moscow 119071, Russian Federation.
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10
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Wilczyński JR, Wilczyński M, Paradowska E. "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies. Front Oncol 2023; 13:1201497. [PMID: 37448521 PMCID: PMC10338102 DOI: 10.3389/fonc.2023.1201497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 06/07/2023] [Indexed: 07/15/2023] Open
Abstract
Ovarian cancer, especially high-grade serous type, is the most lethal gynecological malignancy. The lack of screening programs and the scarcity of symptomatology result in the late diagnosis in about 75% of affected women. Despite very demanding and aggressive surgical treatment, multiple-line chemotherapy regimens and both approved and clinically tested targeted therapies, the overall survival of patients is still unsatisfactory and disappointing. Research studies have recently brought some more understanding of the molecular diversity of the ovarian cancer, its unique intraperitoneal biology, the role of cancer stem cells, and the complexity of tumor microenvironment. There is a growing body of evidence that individualization of the treatment adjusted to the molecular and biochemical signature of the tumor as well as to the medical status of the patient should replace or supplement the foregoing therapy. In this review, we have proposed the principles of the novel regimen of the therapy that we called the "DEPHENCE" system, and we have extensively discussed the results of the studies focused on the ovarian cancer stem cells, other components of cancer metastatic niche, and, finally, clinical trials targeting these two environments. Through this, we have tried to present the evolving landscape of treatment options and put flesh on the experimental approach to attack the high-grade serous ovarian cancer multidirectionally, corresponding to the "DEPHENCE" system postulates.
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Affiliation(s)
- Jacek R Wilczyński
- Department of Gynecological Surgery and Gynecological Oncology, Medical University of Lodz, Lodz, Poland
| | - Miłosz Wilczyński
- Department of Gynecological, Endoscopic and Oncological Surgery, Polish Mother's Health Center-Research Institute, Lodz, Poland
- Department of Surgical and Endoscopic Gynecology, Medical University of Lodz, Lodz, Poland
| | - Edyta Paradowska
- Laboratory of Virology, Institute of Medical Biology of the Polish Academy of Sciences, Lodz, Poland
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11
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Yue M, Guo T, Nie DY, Zhu YX, Lin M. Advances of nanotechnology applied to cancer stem cells. World J Stem Cells 2023; 15:514-529. [PMID: 37424953 PMCID: PMC10324502 DOI: 10.4252/wjsc.v15.i6.514] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/01/2023] [Accepted: 04/18/2023] [Indexed: 06/26/2023] Open
Abstract
Cancer stem cells (CSCs) are a small proportion of the cells that exist in cancer tissues. They are considered to be the culprit of tumor genesis, development, drug resistance, metastasis and recurrence because of their self-renewal, proliferation, and differentiation potential. The elimination of CSCs is thus the key to cure cancer, and targeting CSCs provides a new method for tumor treatment. Due to the advantages of controlled sustained release, targeting and high biocompatibility, a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs. This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs. Furthermore, we identify the problems and future research directions of nanotechnology in CSC therapy. We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.
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Affiliation(s)
- Miao Yue
- Clinical Laboratory, Nanjing University of Chinese Medicine, Taizhou 225300, Jiangsu Province, China
| | - Ting Guo
- Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu Province, China
| | - Deng-Yun Nie
- Clinical Laboratory, Nanjing University of Chinese Medicine, Taizhou 225300, Jiangsu Province, China
| | - Yin-Xing Zhu
- Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu Province, China
| | - Mei Lin
- Taizhou School of Clinical Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou 225300, Jiangsu Province, China.
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12
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Malik SB, Gul A, Saggu JI, Abbasi BA, Azad B, Iqbal J, Kazi M, Chalgham W, Firoozabadi SAM. Fabrication and Characterization of Ag-Graphene Nanocomposites and Investigation of Their Cytotoxic, Antifungal and Photocatalytic Potential. Molecules 2023; 28:molecules28104139. [PMID: 37241880 DOI: 10.3390/molecules28104139] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/11/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
In the present study, we aimed to synthesize (Ag)1-x(GNPs)x nanocomposites in variable ratios (25% GNPs-Ag, 50% GNPs-Ag, and 75% GNPs-Ag) via an ex situ approach to investigate the incremental effects of GNPs (graphene nanoparticles) on AgNPs (silver nanoparticles). The prepared nanocomposites were successfully characterized using different microscopic and spectroscopic techniques, including X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, ultraviolet spectroscopy, and Raman spectroscopic analysis. For the evaluation of morphological aspects, shape, and percentage elemental composition, SEM and EDX analyses were employed. The bioactivities of the synthesized nanocomposites were briefly investigated. The antifungal activity of (Ag)1-x(GNPs)x nanocomposites was reported to be 25% for AgNPs and 66.25% using 50% GNPs-Ag against Alternaria alternata. The synthesized nanocomposites were further evaluated for cytotoxic potential against U87 cancer cell lines with improved results (for pure AgNPs IC50: ~150 µg/mL, for 50% GNPs-Ag IC50: ~12.5 µg/mL). The photocatalytic properties of the nanocomposites were determined against the toxic dye Congo red, and the percentage degradation was recorded as 38.35% for AgNPs and 98.7% for 50% GNPs-Ag. Hence, from the results, it is concluded that silver nanoparticles with carbon derivatives (graphene) have strong anticancer and antifungal properties. Dye degradation strongly confirmed the photocatalytic potential of Ag-graphene nanocomposites in the removal of toxicity present in organic water pollutants.
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Affiliation(s)
- Sidra Batool Malik
- Department of Biological Sciences, International Islamic University, Islamabad 44000, Pakistan
| | - Asma Gul
- Department of Biological Sciences, International Islamic University, Islamabad 44000, Pakistan
| | - Javed Iqbal Saggu
- Department of Physics, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Banzeer Ahsan Abbasi
- Department of Botany, Rawalpindi Women University, 6th Road, Satellite Town, Rawalpindi 46300, Pakistan
| | - Beenish Azad
- Department of Biological Sciences, International Islamic University, Islamabad 44000, Pakistan
| | - Javed Iqbal
- 2Department of Botany, Bacha Khan University, Charsadda 24420, Pakistan
| | - Mohsin Kazi
- Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
| | - Wadie Chalgham
- Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, CA 90095, USA
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13
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Shen F, Wang G, Liu X, Zhu S. Exogenous inoculation of endophyte Penicillium sp. alleviated pineapple internal browning during storage. Heliyon 2023; 9:e16258. [PMID: 37234623 PMCID: PMC10205634 DOI: 10.1016/j.heliyon.2023.e16258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Accepted: 05/11/2023] [Indexed: 05/28/2023] Open
Abstract
Pineapple is ranked sixth in terms of global fruit production and the most traded tropical fruit worldwide. Internal browning (IB), a physiological disorder of pineapple fruit after harvest, limits the export and industry development of pineapple. Evidence confirmed that endophyte played a pivotal role in plant disease. This study investigated the relationship between endophyte fungi community structure, population abundance in healthy and IB pineapple fruit; as well as the effect of endophyte Penicillium sp. inoculation on pineapple IB. Intended to explore a new effective measure for controlling IB and reducing postharvest losses in pineapple by an economical and environmentally friendly approach. We found the abundance of endophyte fungi in healthy pineapple fruit was different from that in IB fruit by high-throughput sequencing. The results emphasized that the endophyte Penicillium sp. inoculation dramatically alleviated pineapple IB intensity and severity, delayed crown withering and fruit yellowing, and maintained the exterior quality traits during the postharvest period at 20 °C. Penicillium sp. retarded H2O2 accumulation and increased the total phenols level in pineapple. Application of Penicillium sp. also maintained the higher antioxidant capacity by increasing antioxidant enzyme activity and ascorbic acids levels, regulated of the homeostasis of endogenous hormones, and increased the abundance of Penicillium sp. in the fruit. In summary, Penicillium sp. retarded the occurrence of IB and enhanced the storability of pineapple at postharvest, and this economical and environmentally friendly technology is convenient to spread in agriculture.
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Affiliation(s)
| | | | | | - Shijiang Zhu
- Corresponding author. 483 Wushan Road, Tianhe District, South China Agricultural University, Guangzhou, 510640, China.
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14
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Procoxacin bidirectionally inhibits osteoblastic and osteoclastic activity in bone and suppresses bone metastasis of prostate cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2023; 42:45. [PMID: 36759880 PMCID: PMC9909988 DOI: 10.1186/s13046-023-02610-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Accepted: 01/21/2023] [Indexed: 02/11/2023]
Abstract
BACKGROUND Bone is the most common site of metastasis of prostate cancer (PCa). PCa invasion leads to a disruption of osteogenic-osteolytic balance and causes abnormal bone formation. The interaction between PCa and bone stromal cells, especially osteoblasts (OB), is considered essential for the disease progression. However, drugs that effectively block the cancer-bone interaction and regulate the osteogenic-osteolytic balance remain undiscovered. METHODS A reporter gene system was constructed to screen compounds that could inhibit PCa-induced OB activation from 631 compounds. Then, the pharmacological effects of a candidate drug, Procoxacin (Pro), on OBs, osteoclasts (OCs) and cancer-bone interaction were studied in cellular models. Intratibial inoculation, micro-CT and histological analysis were used to explore the effect of Pro on osteogenic and osteolytic metastatic lesions. Bioinformatic analysis and experiments including qPCR, western blotting and ELISA assay were used to identify the effector molecules of Pro in the cancer-bone microenvironment. Virtual screening, molecular docking, surface plasmon resonance assay and RNA knockdown were utilized to identify the drug target of Pro. Experiments including co-IP, western blotting and immunofluorescence were performed to reveal the role of Pro binding to its target. Intracardiac inoculation metastasis model and survival analysis were used to investigate the therapeutic effect of Pro on metastatic cancer. RESULTS Luciferase reporter gene consisted of Runx2 binding sequence, OSE2, and Alp promotor could sensitively reflect the intensity of PCa-OB interaction. Pro best matched the screening criteria among 631 compounds in drug screening. Further study demonstrated that Pro effectively inhibited the PCa-induced osteoblastic changes without killing OBs or PCa cells and directly killed OCs or suppressed osteoclastic functions at very low concentrations. Mechanism study revealed that Pro broke the feedback loop of TGF-β/C-Raf/MAPK pathway by sandwiching into 14-3-3ζ/C-Raf complex and prevented its disassociation. Pro treatment alleviated both osteogenic and osteolytic lesions in PCa-involved bones and reduced the number of metastases of PCa in vivo. CONCLUSIONS In summary, our study provides a drug screening strategy based on the cancer-host microenvironment and demonstrates that Pro effectively inhibits both osteoblastic and osteoclastic lesions in PCa-involved bones, which makes it a promising therapeutic agent for PCa bone metastasis.
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15
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Taheriazam A, Abad GGY, Hajimazdarany S, Imani MH, Ziaolhagh S, Zandieh MA, Bayanzadeh SD, Mirzaei S, Hamblin MR, Entezari M, Aref AR, Zarrabi A, Ertas YN, Ren J, Rajabi R, Paskeh MDA, Hashemi M, Hushmandi K. Graphene oxide nanoarchitectures in cancer biology: Nano-modulators of autophagy and apoptosis. J Control Release 2023; 354:503-522. [PMID: 36641122 DOI: 10.1016/j.jconrel.2023.01.028] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 01/08/2023] [Accepted: 01/09/2023] [Indexed: 01/16/2023]
Abstract
Nanotechnology is a growing field, with many potential biomedical applications of nanomedicine for the treatment of different diseases, particularly cancer, on the horizon. Graphene oxide (GO) nanoparticles can act as carbon-based nanocarriers with advantages such as a large surface area, good mechanical strength, and the capacity for surface modification. These nanostructures have been extensively used in cancer therapy for drug and gene delivery, photothermal therapy, overcoming chemotherapy resistance, and for imaging procedures. In the current review, we focus on the biological functions of GO nanoparticles as regulators of apoptosis and autophagy, the two major forms of programmed cell death. GO nanoparticles can either induce or inhibit autophagy in cancer cells, depending on the conditions. By stimulating autophagy, GO nanocarriers can promote the sensitivity of cancer cells to chemotherapy. However, by impairing autophagy flux, GO nanoparticles can reduce cell survival and enhance inflammation. Similarly, GO nanomaterials can increase ROS production and induce DNA damage, thereby sensitizing cancer cells to apoptosis. In vitro and in vivo experiments have investigated whether GO nanomaterials show any toxicity in major body organs, such as the brain, liver, spleen, and heart. Molecular pathways, such as ATG, MAPK, JNK, and Akt, can be regulated by GO nanomaterials, leading to effects on autophagy and apoptosis. These topics are discussed in this review to shed some lights towards the biomedical potential of GO nanoparticles and their biocompatibility, paving the way for their future application in clinical trials.
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Affiliation(s)
- Afshin Taheriazam
- Department of Orthopedics, Faculty of medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran
| | - Ghazaleh Gholamiyan Yousef Abad
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Shima Hajimazdarany
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Cellular and Molecular Biology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mohammad Hassan Imani
- Department of Clinical Science, Faculty of Veterinary Medicine, Islamic Azad University, Shahr-e kord Branch, Chaharmahal and Bakhtiari, Iran
| | - Setayesh Ziaolhagh
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mohammad Arad Zandieh
- Department of Food Hygiene and Quality Control, Division of epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
| | | | - Sepideh Mirzaei
- Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein 2028, South Africa; Radiation Biology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Amir Reza Aref
- Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Vice President at Translational Sciences, Xsphera Biosciences Inc., 6 Tide Street, Boston, MA, 02210, USA
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Turkey
| | - Yavuz Nuri Ertas
- Department of Biomedical Engineering, Erciyes University, Kayseri, Turkey; ERNAM-Nanotechnology Research and Application Center, Erciyes University, Kayseri, Turkey
| | - Jun Ren
- Shanghai Institute of Cardiovascular Diseases, Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Romina Rajabi
- Faculty of Veterinary Medicine, Islamic Azad University, Science and Research Branch, Tehran, Iran.
| | - Mahshid Deldar Abad Paskeh
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Kiavash Hushmandi
- Department of Food Hygiene and Quality Control, Division of epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
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Current Update on Nanotechnology-Based Approaches in Ovarian Cancer Therapy. Reprod Sci 2023; 30:335-349. [PMID: 35585292 DOI: 10.1007/s43032-022-00968-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 05/06/2022] [Indexed: 10/18/2022]
Abstract
Ovarian cancer is one of the leading causes of cancer-related deaths among women. The drawbacks of conventional therapeutic strategies encourage researchers to look for alternative strategies, including nanotechnology. Nanotechnology is one of the upcoming domains of science that is rechanneled towards targeted cancer therapy and diagnosis. Nanocarriers such as dendrimers, liposomes, polymer micelles, and polymer nanoparticles present distinct surface characteristics in morphology, surface chemistry, and mode of action that help differentiate normal and malignant cells, which paves the way for target-specific drug delivery. Similarly, nanoparticles have been strategically utilized as efficacious vehicles to deliver drugs that alter the epigenetic modifications in epigenetic therapy. Some studies suggest that the use of specialized target-modified nanoparticles in siRNA-based nanotherapy prevents internalization and improves the antitumor activity of siRNA by ensuring unrestrained entry of siRNA into the tumor vasculature and efficient intracellular delivery of siRNA. Moreover, research findings highlight the significance of utilizing nanoparticles as depots for photosensitive drugs in photodynamic therapy. The applicability of nanoparticles is further extended to medical imaging. They serve as contrast agents in combination with conventional imaging modalities such as MRI, CT, and fluorescence-based imaging to produce vivid and enhanced images of tumors. Therefore, this review aims to explore and delve deeper into the advent of various nanotechnology-based therapeutic and imaging techniques that provide non-invasive and effective means to tackle ovarian cancers.
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Vimalanathan B, Vijaya JJ, Mary BCJ, Mary RN, Km M, Jayavel R, Abumousa RA, Bououdina M. The Cytotoxic Effectiveness of Thiourea-Reduced Graphene Oxide on Human Lung Cancer Cells and Fungi. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 13:149. [PMID: 36616058 PMCID: PMC9823875 DOI: 10.3390/nano13010149] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/20/2022] [Accepted: 12/23/2022] [Indexed: 06/17/2023]
Abstract
This study demonstrated the effective reduction of graphene oxide (GO) by employing thiourea as a reducing and stabilizing agent. Two fungi (Aspergillus flavus and Aspergillus fumigatus) were used for anti-fungal assay. Cell viability, cell cycle analysis, DNA fragmentation, and cell morphology were assessed to determine the toxicity of thiourea-reduced graphene oxide (T-rGO) on human lung cancer cells. The results revealed that GO and T-rGO were hazardous to cells in a dose-dependent trend. The viability of both A. fumigatus and A. flavus was affected by GO and T-rGO. The reactive oxygen species produced by T-rGO caused the death of A. flavus and A. fumigatus cells. This study highlighted the effectiveness of T-rGO as an antifungal agent. In addition, T-rGO was found to be more harmful to cancer cells than GO. Thus, T-rGO manifested great potential in biological and biomedical applications.
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Affiliation(s)
- Babu Vimalanathan
- Crystal Growth Centre, Anna University, Chennai 600025, Tamil Nadu, India
| | - J. Judith Vijaya
- Catalysis and Nanomaterials Research Laboratory, Department of Chemistry, Loyola College, Chennai 600034, Tamil Nadu, India
| | - B. Carmel Jeeva Mary
- Catalysis and Nanomaterials Research Laboratory, Department of Chemistry, Loyola College, Chennai 600034, Tamil Nadu, India
| | - Ruby Nirmala Mary
- Crystal Growth Centre, Anna University, Chennai 600025, Tamil Nadu, India
| | - Mohamed Km
- Catalysis and Nanomaterials Research Laboratory, Department of Chemistry, Loyola College, Chennai 600034, Tamil Nadu, India
| | - Ramasamy Jayavel
- Crystal Growth Centre, Anna University, Chennai 600025, Tamil Nadu, India
| | - Rasha A. Abumousa
- Department of Mathematics and Sciences, College of Humanities and Sciences, Prince Sultan University, Riyadh 11586, Saudi Arabia
| | - Mohamed Bououdina
- Department of Mathematics and Sciences, College of Humanities and Sciences, Prince Sultan University, Riyadh 11586, Saudi Arabia
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Gurunathan S, Kim JH. Graphene Oxide Enhances Biogenesis and Release of Exosomes in Human Ovarian Cancer Cells. Int J Nanomedicine 2022; 17:5697-5731. [PMID: 36466784 PMCID: PMC9717435 DOI: 10.2147/ijn.s385113] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Accepted: 11/04/2022] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND Exosomes, which are nanovesicles secreted by almost all the cells, mediate intercellular communication and are involved in various physiological and pathological processes. We aimed to investigate the effects of graphene oxide (GO) on the biogenesis and release of exosomes in human ovarian cancer (SKOV3) cells. METHODS Exosomes were isolated using ultracentrifugation and ExoQuick and characterized by various analytical techniques. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS Graphene oxide (10-50 μg/mL), cisplatin (2-10 μg/mL), and C6-ceramide (5-25 μM) inhibited the cell viability, proliferation, and cytotoxicity in a dose-dependent manner. We observed that graphene oxide (GO), cisplatin (CIS), and C6-Ceramide (C6-Cer) stimulated acetylcholine esterase and neutral sphingomyelinase activity, total exosome protein concentration, and exosome counts associated with increased level of apoptosis, oxidative stress and endoplasmic reticulum stress. In contrast, GW4869 treatment inhibits biogenesis and release of exosomes. We observed that the human ovarian cancer cells secreted exosomes with typical cup-shaped morphology and surface protein biomarkers. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in GO-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from GO-treated SKOV3 cells than in those isolated from control cells. SKOV3 cells pre-treated with N-acetylcysteine or GW4869 displayed a significant reduction in GO-induced exosome biogenesis and release. Furthermore, endocytic inhibitors decrease exosome biogenesis and release by impairing endocytic pathways. CONCLUSION This study identifies GO as a potential tool for targeting the exosome pathway and stimulating exosome biogenesis and release. We believe that the knowledge acquired in this study can be potentially extended to other exosome-dominated pathologies and model systems. Furthermore, these nanoparticles can provide a promising means to enhance exosome production in SKOV3 cells.
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Affiliation(s)
- Sangiliyandi Gurunathan
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea
| | - Jin Hoi Kim
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, 05029, Korea
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19
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Nayak A, Warrier NM, Kumar P. Cancer Stem Cells and the Tumor Microenvironment: Targeting the Critical Crosstalk through Nanocarrier Systems. Stem Cell Rev Rep 2022; 18:2209-2233. [PMID: 35876959 PMCID: PMC9489588 DOI: 10.1007/s12015-022-10426-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/10/2022] [Indexed: 11/25/2022]
Abstract
The physiological state of the tumor microenvironment (TME) plays a central role in cancer development due to multiple universal features that transcend heterogeneity and niche specifications, like promoting cancer progression and metastasis. As a result of their preponderant involvement in tumor growth and maintenance through several microsystemic alterations, including hypoxia, oxidative stress, and acidosis, TMEs make for ideal targets in both diagnostic and therapeutic ventures. Correspondingly, methodologies to target TMEs have been investigated this past decade as stratagems of significant potential in the genre of focused cancer treatment. Within targeted oncotherapy, nanomedical derivates-nanocarriers (NCs) especially-have emerged to present notable prospects in enhancing targeting specificity. Yet, one major issue in the application of NCs in microenvironmental directed therapy is that TMEs are too broad a spectrum of targeting possibilities for these carriers to be effectively employed. However, cancer stem cells (CSCs) might portend a solution to the above conundrum: aside from being quite heavily invested in tumorigenesis and therapeutic resistance, CSCs also show self-renewal and fluid clonogenic properties that often define specific TME niches. Further scrutiny of the relationship between CSCs and TMEs also points towards mechanisms that underly tumoral characteristics of metastasis, malignancy, and even resistance. This review summarizes recent advances in NC-enabled targeting of CSCs for more holistic strikes against TMEs and discusses both the current challenges that hinder the clinical application of these strategies as well as the avenues that can further CSC-targeting initiatives. Central role of CSCs in regulation of cellular components within the TME.
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Affiliation(s)
- Aadya Nayak
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Neerada Meenakshi Warrier
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India
| | - Praveen Kumar
- Department of Biotechnology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
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Srimurugan S, K Ravi A, Vijaya Anand A, Muthukrishnan S. Biosynthesis of silver nanoparticles using Citrus hystrix leaf extract and evaluation of its anticancer efficacy against HeLa cell line. Drug Dev Ind Pharm 2022; 48:480-490. [PMID: 36165580 DOI: 10.1080/03639045.2022.2130352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
BACKGROUND Cervical cancer continues to be the leading cause of death worldwide despite the availability of many therapeutic options. Biogenic synthesis of metal nanoparticles paves a new way for the development of targeted drug delivery modalities of cancer therapeutics. OBJECTIVE In this study, we demonstrate the efficacy of biosynthesized silver nanoparticles from methanolic leaf extract of Citrus hystrix as an anticancer agent used against cervical cancer cell line HeLa. METHODS The addition of 1mM silver nitrate to methanolic leaf extract of Citrus hystrix resulted in the biosynthesis of silver nanoparticles during the reaction mixture and was incubated in the dark for 1 hour at pH 9 with gentle stirring. Characterization of synthesized NPs was carried out using various analyses. MTT assay, DAPI, AO/EB double staining and RT-PCR analysis were carried out to evaluate the cytotoxic activity of ChAgNPs. RESULTS AND CONCLUSION The absorption band at 430 nm, as shown by UV-Vis spectroscopy revealed the formation of AgNPs. SEM and TEM analysis shows that most of the ChAgNPs were spherical in shape and XRD patterns revealed the crystalline nature of the particles. Moreover, its potent cytotoxic effect on the HeLa cell line was analyzed using MTT assay with an IC50 value of 56 µg/ml by decreasing the cell viability in a dose and time-dependent manner. The induced apoptotic activity was confirmed by DAPI and double staining methods. Autophagic and apoptotic mediated cell death in ChAgNPs treated HeLa cell line were confirmed by staining procedures and RT-PCR methods.
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Affiliation(s)
- Swetha Srimurugan
- Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, India
| | - Anjali K Ravi
- Department of Biochemistry, Bharathiar University, Coimbatore, Tamil Nadu, India
| | - Arumugam Vijaya Anand
- Department of Human Genetics and Molecular Genetics, Bharathiar University, Coimbatore, Tamil Nadu, India
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21
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Wang J, Liu N, Su Q, Lv Y, Yang C, Zhan H. Green Synthesis of Gold Nanoparticles and Study of Their Inhibitory Effect on Bulk Cancer Cells and Cancer Stem Cells in Breast Carcinoma. NANOMATERIALS (BASEL, SWITZERLAND) 2022; 12:nano12193324. [PMID: 36234451 PMCID: PMC9565927 DOI: 10.3390/nano12193324] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Revised: 09/16/2022] [Accepted: 09/21/2022] [Indexed: 05/29/2023]
Abstract
Chemo-resistance from cancer stem cells (CSCs) subpopulation is a current issue in cancer treatment. It is important to select alternative therapies to efficiently eradicate both bulk cancer cells and CSCs. Here, gold nanoparticles (AuNPs) have been selected regarding their biocompatibility, facile and controllable synthesis, potent anti-cancer activity and photothermal conversion performance. We reported a green synthesis of functionalized AuNPs using hyaluronic acid (HA) as a reductant, capping, stabilizing and hydrophilic substance. The resultant AuNPs were spherical-shaped with an average diameter of around 30 nm. These AuNPs displayed improved physico-chemical (yield, stability, photothermal effect) and biological properties (cellular uptake, cytotoxicity and apoptotic effect) against bulk MDA-MB-231 cells, in comparison with other organic anti-cancer drugs. The intensified bioactivity was dependent on a mitochondria-mediated cascade, reflected by the damage in mitochondria, oxidative stress, intensified Caspase 3 activity and increased/decreased expression of certain pro-apoptotic (Bax, P53, Caspase 3)/anti-apoptotic (Bcl-2) genes. Moreover, these AuNPs posed a dramatically improved inhibitory effect in cell viability and self-renewable capacity on CSC subpopulation. All the results were attributed from the nano-scaled structure of AuNPs and combined effect from NIR-induced hyperthermia. In addition, the biocompatible nature of these AuNPs supported them to be a potential candidate in the development of novel chemotherapeutic drugs.
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Affiliation(s)
- Jihui Wang
- School of Chemical Engineering and Energy Technology, Dongguan University of Technology, Dongguan 523808, China
- Department of Bioengineering, School of Bioengineering, Dalian Polytechnic University, Dalian 116034, China
| | - Na Liu
- Department of Bioengineering, School of Bioengineering, Dalian Polytechnic University, Dalian 116034, China
| | - Qing Su
- Department of Bioengineering, School of Bioengineering, Dalian Polytechnic University, Dalian 116034, China
| | - Yulong Lv
- Department of Bioengineering, School of Bioengineering, Dalian Polytechnic University, Dalian 116034, China
| | - Chang Yang
- Department of Bioengineering, School of Bioengineering, Dalian Polytechnic University, Dalian 116034, China
| | - Honglei Zhan
- Department of Bioengineering, School of Bioengineering, Dalian Polytechnic University, Dalian 116034, China
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22
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Vimalanathan B, Vijaya JJ, Mary BCJ, Ignacimuthu S, Daniel M, Jayavel R, Bououdina M, Bellucci S. The Anticancer Efficacy of Thiourea-Mediated Reduced Graphene Oxide Nanosheets against Human Colon Cancer Cells (HT-29). J Funct Biomater 2022; 13:jfb13030130. [PMID: 36135565 PMCID: PMC9502518 DOI: 10.3390/jfb13030130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 08/20/2022] [Accepted: 08/23/2022] [Indexed: 01/03/2023] Open
Abstract
The current research focuses on the fabrication of water-soluble, reduced graphene oxide (rGO) employing thiourea (T) using a simple cost-effective method, and subsequently examining its anticancer characteristics. The cytotoxicity caused by graphene oxide (GO) and T-rGO is investigated in detail. Biological results reveal a concentration-dependent toxicity of GO and T-rGO in human colon cancer cells HT-29. A decrease in cell viability alongside DNA fragmentation is observed. Flow cytometry analysis confirms the cytotoxic effects. The novelty in this work is the use of raw graphite powder, and oxidants such as KMNO4, NaNO3, and 98 percent H2SO4 to produce graphene oxide by a modified Hummers method. This study demonstrates a simple and affordable procedure for utilising thiourea to fabricate a water-soluble reduced graphene oxide, which will be useful in a variety of biomedical applications.
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Affiliation(s)
| | - J. Judith Vijaya
- Catalysis and Nanomaterials Research Laboratory, Department of Chemistry, Loyola College, Chennai 600034, India
- Correspondence: (J.J.V.); (R.J.)
| | - B. Carmel Jeeva Mary
- Catalysis and Nanomaterials Research Laboratory, Department of Chemistry, Loyola College, Chennai 600034, India
| | | | - Magesh Daniel
- Department of Zoology, Loyola College, Chennai 600034, India
| | - Ramasamy Jayavel
- Crystal Growth Centre, Anna University, Chennai 600025, India
- Correspondence: (J.J.V.); (R.J.)
| | - Mohamed Bououdina
- Department of Mathematics and Sciences, Faculty of Humanities and Sciences, Prince Sultan University, Riyadh 122001, Saudi Arabia
| | - Stefano Bellucci
- INFN-Laboratori Nazionali di Frascati, Via E. Fermi 54, 00044 Frascati, Italy
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23
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Synthesis and Characterization of Silver and Graphene Nanocomposites and Their Antimicrobial and Photocatalytic Potentials. Molecules 2022; 27:molecules27165184. [PMID: 36014424 PMCID: PMC9415913 DOI: 10.3390/molecules27165184] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/10/2022] [Accepted: 06/17/2022] [Indexed: 11/30/2022] Open
Abstract
Microbial pathogens and bulk amounts of industrial toxic wastes in water are an alarming situation to humans and a continuous threat to aquatic life. In this study, multifunctional silver and graphene nanocomposites (Ag)1−x(GNPs)x [25% (x = 0.25), 50% (x = 0.50) and 75% (x = 0.75) of GNPs] were synthesized via ex situ approach. Further, the synthesized nanocomposites were explored for their physicochemical characteristics, such as vibrational modes (Raman spectroscopic analysis), optical properties (UV visible spectroscopic analysis), antibacterial and photocatalytic applications. We investigated the antimicrobial activity of silver and graphene nanocomposites (Ag-GNPs), and the results showed that Ag-GNPs nanocomposites exhibit remarkably improved antimicrobial activity (28.78% (E. coli), 31.34% (S. aureus) and 30.31% (P. aeruginosa) growth inhibition, which might be due to increase in surface area of silver nanoparticles (AgNPs)). Furthermore, we investigated the photocatalytic activity of silver (AgNPs) and graphene (GNPs) nanocomposites in varying ratios. Interestingly, the Ag-GNPs nanocomposites show improved photocatalytic activity (78.55% degradation) as compared to AgNPs (54.35%), which can be an effective candidate for removing the toxicity of dyes. Hence, it is emphatically concluded that Ag-GNPs hold very active behavior towards the decolorization of dyes and could be a potential candidate for the treatment of wastewater and possible pathogenic control over microbes. In the future, we also recommend different other in vitro biological and environmental applications of silver and graphene nanocomposites.
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24
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The Preliminary Study on the Proapoptotic Effect of Reduced Graphene Oxide in Breast Cancer Cell Lines. Int J Mol Sci 2021; 22:ijms222212593. [PMID: 34830472 PMCID: PMC8620501 DOI: 10.3390/ijms222212593] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 11/16/2021] [Accepted: 11/19/2021] [Indexed: 01/10/2023] Open
Abstract
Breast cancer is the most common cancer diagnosed in women, however traditional therapies have several side effects. This has led to an urgent need to explore novel drug approaches to treatment strategies such as graphene-based nanomaterials such as reduced graphene oxide (rGO). It was noticed as a potential drug due to its target selectivity, easy functionalisation, chemisensitisation, and high drug-loading capacity. rGO is widely used in many fields, including biological and biomedical, due to its unique physicochemical properties. However, the possible mechanisms of rGO toxicity remain unclear. In this paper, we present findings on the cytotoxic and antiproliferative effects of rGO and its ability to induce oxidative stress and apoptosis of breast cancer cell lines. We indicate that rGO induced time- and dose-dependent cytotoxicity in MDA-MB-231 and ZR-75-1 cell lines, but not in T-47D, MCF-7, Hs 578T cell lines. In rGO-treated MDA-MB-231 and ZR-75-1 cell lines, we noticed increased induction of apoptosis and necrosis. In addition, rGO has been found to cause oxidative stress, reduce proliferation, and induce structural changes in breast cancer cells. Taken together, these studies provide new insight into the mechanism of oxidative stress and apoptosis in breast cancer cells.
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25
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Qi D, Liu Y, Li J, Huang JH, Hu X, Wu E. Salinomycin as a potent anticancer stem cell agent: State of the art and future directions. Med Res Rev 2021; 42:1037-1063. [PMID: 34786735 PMCID: PMC9298915 DOI: 10.1002/med.21870] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 10/22/2021] [Accepted: 10/26/2021] [Indexed: 12/11/2022]
Abstract
Cancer stem cells (CSCs) are a small subpopulation of cells within a tumor that can both self‐renew and differentiate into other cell types forming the heterogeneous tumor bulk. Since CSCs are involved in all aspects of cancer development, including tumor initiation, cell proliferation, metastatic dissemination, therapy resistance, and recurrence, they have emerged as attractive targets for cancer treatment and management. Salinomycin, a widely used antibiotic in poultry farming, was identified by the Weinberg group as a potent anti‐CSC agent in 2009. As a polyether ionophore, salinomycin exerts broad‐spectrum activities, including the important anti‐CSC function. Studies on the mechanism of action of salinomycin against cancer have been continuously and rapidly published since then. Thus, it is imperative for us to update its literature of recent research findings in this area. We here summarize the notable work reported on salinomycin's anticancer activities, intracellular binding target(s), effects on tumor microenvironment, safety, derivatives, and tumor‐specific drug delivery; after that we also discuss the translational potential of salinomycin toward clinical application based on current multifaceted understandings.
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Affiliation(s)
- Dan Qi
- Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, USA.,Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, USA
| | - Yunyi Liu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China
| | - Juan Li
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China
| | - Jason H Huang
- Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, USA.,Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, USA.,Department of Surgery, Texas A&M University College of Medicine, Temple, Texas, USA
| | - Xiaoxiao Hu
- Molecular Science and Biomedicine Laboratory, State Key Laboratory for Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Collaborative Innovation Center for Molecular Engineering for Theranostics, Hunan University, Changsha, China.,Shenzhen Research Institute, Hunan University, Shenzhen, Guangdong, China
| | - Erxi Wu
- Department of Neurosurgery, Baylor Scott & White Health, Temple, Texas, USA.,Neuroscience Institute, Baylor Scott & White Health, Temple, Texas, USA.,Department of Surgery, Texas A&M University College of Medicine, Temple, Texas, USA.,LIVESTRONG Cancer Institutes and Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, Texas, USA.,Department of Pharmaceutical Sciences, Texas A&M University College of Pharmacy, College Station, Texas, USA
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26
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Ma Y, Wang J, Wu J, Tong C, Zhang T. Meta-analysis of cellular toxicity for graphene via data-mining the literature and machine learning. THE SCIENCE OF THE TOTAL ENVIRONMENT 2021; 793:148532. [PMID: 34328986 DOI: 10.1016/j.scitotenv.2021.148532] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Revised: 06/13/2021] [Accepted: 06/14/2021] [Indexed: 06/13/2023]
Abstract
Since graphene is currently incorporated into various consumer products and used in a variety of applications, determining the relationships between the physicochemical properties of graphene and its toxicity is critical for conducting environmental and health risk analyses. Data from the literature suggest that exposure to graphene may result in cytotoxicity. However, existing graphene toxicity data are complex and heterogeneous, making it difficult to conduct risk assessments. Here, we conducted a meta-analysis of published data on the cytotoxicity of graphene based on 792 publications, including 986 cell viability data points, 762 half maximal inhibitory concentration (IC50) data points, and 100 lactate dehydrogenase (LDH) release data points. Models to predict graphene cytotoxicity were then developed based on cell viability, IC50, and LDH release as toxicity endpoints using random forests learning algorithms. The most influential attributes influencing graphene cytotoxicity were revealed to be exposure dose and detection method for cell viability, diameter and surface modification for IC50, and detection method and organ source for LDH release. The meta-analysis produced three sets of key attributes for the three abovementioned toxicity endpoints that can be used in future studies of graphene toxicity. The findings indicate that rigorous data mining protocols can be combined with suitable machine learning tools to develop models with good predictive power and accuracy. The results also provide guidance for the design of safe graphene materials.
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Affiliation(s)
- Ying Ma
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Jianli Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Jingying Wu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China
| | - Chuxuan Tong
- School of Information Technology and Electrical Engineering, The University of Queensland Brisbane, QLD 4072, Australia
| | - Ting Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
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27
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Cao J, Bhatnagar S, Wang J, Qi X, Prabha S, Panyam J. Cancer stem cells and strategies for targeted drug delivery. Drug Deliv Transl Res 2021; 11:1779-1805. [PMID: 33095384 PMCID: PMC8062588 DOI: 10.1007/s13346-020-00863-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/01/2020] [Indexed: 12/23/2022]
Abstract
Cancer stem cells (CSCs) are a small proportion of cancer cells with high tumorigenic activity, self-renewal ability, and multilineage differentiation potential. Standard anti-tumor therapies including conventional chemotherapy, radiation therapy, and molecularly targeted therapies are not effective against CSCs, and often lead to enrichment of CSCs that can result in tumor relapse. Therefore, it is hypothesized that targeting CSCs is key to increasing the efficacy of cancer therapies. In this review, CSC properties including CSC markers, their role in tumor growth, invasiveness, metastasis, and drug resistance, as well as CSC microenvironment are discussed. Further, CSC-targeted strategies including the use of targeted drug delivery systems are examined.
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Affiliation(s)
- Jin Cao
- School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
- College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA
| | - Shubhmita Bhatnagar
- College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA
- School of Pharmacy, Temple University, Philadelphia, PA, 19140, USA
| | - Jiawei Wang
- College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA
- College of Pharmacy, University of Texas at Austin, Austin, TX, 78712, USA
| | - Xueyong Qi
- School of Pharmacy, Jiangsu University, Zhenjiang, 212013, Jiangsu, China
| | - Swayam Prabha
- College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA
- Cancer Research & Molecular Biology and Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA
| | - Jayanth Panyam
- College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA.
- School of Pharmacy, Temple University, Philadelphia, PA, 19140, USA.
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28
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Micale N, Molonia MS, Citarella A, Cimino F, Saija A, Cristani M, Speciale A. Natural Product-Based Hybrids as Potential Candidates for the Treatment of Cancer: Focus on Curcumin and Resveratrol. Molecules 2021; 26:4665. [PMID: 34361819 PMCID: PMC8348089 DOI: 10.3390/molecules26154665] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 07/20/2021] [Accepted: 07/28/2021] [Indexed: 02/07/2023] Open
Abstract
One of the main current strategies for cancer treatment is represented by combination chemotherapy. More recently, this strategy shifted to the "hybrid strategy", namely the designing of a new molecular entity containing two or more biologically active molecules and having superior features compared with the individual components. Moreover, the term "hybrid" has further extended to innovative drug delivery systems based on biocompatible nanomaterials and able to deliver one or more drugs to specific tissues or cells. At the same time, there is an increased interest in plant-derived polyphenols used as antitumoral drugs. The present review reports the most recent and intriguing research advances in the development of hybrids based on the polyphenols curcumin and resveratrol, which are known to act as multifunctional agents. We focused on two issues that are particularly interesting for the innovative chemical strategy involved in their development. On one hand, the pharmacophoric groups of these compounds have been used for the synthesis of new hybrid molecules. On the other hand, these polyphenols have been introduced into hybrid nanomaterials based on gold nanoparticles, which have many potential applications for both drug delivery and theranostics in chemotherapy.
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Affiliation(s)
| | | | | | | | - Antonina Saija
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, Italy; (N.M.); (M.S.M.); (A.C.); (F.C.); (M.C.); (A.S.)
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29
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Esmaeili SA, Sahranavard S, Salehi A, Bagheri V. Selectively targeting cancer stem cells: Current and novel therapeutic strategies and approaches in the effective eradication of cancer. IUBMB Life 2021; 73:1045-1059. [PMID: 34184810 DOI: 10.1002/iub.2524] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 06/22/2021] [Accepted: 06/23/2021] [Indexed: 12/19/2022]
Abstract
Cancer stem cells (CSCs) are a subgroup of cells in malignant cancers, which possess self-renewal capacity, tumor-initiating capability, and pluripotency, as well as being responsible for tumor maintenance, metastasis, relapse, and chemoresistance. The treatment modalities previously established for cancer included surgery, chemotherapy, and radiotherapy. The majority of tumor cells of non-CSCs could be eradicated using conventional chemotherapy and radiotherapy. Therefore, novel and promising therapeutic strategies that selectively target CSCs are of great importance. In this review, we described different therapeutic strategies such as immunotherapy, metabolism-based therapeutic strategies, and additional potential therapeutic approaches (targeting microRNAs [miRNAs], histone deacetylase, and DNA methyl transferase) against CSCs. Taken together, due to the inefficiency of anticancer single therapies, targeting CSCs through their metabolism and using immunotherapy and miRNAs besides classical chemo- and radiotherapy may exert better therapeutic effects.
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Affiliation(s)
- Seyed-Alireza Esmaeili
- Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.,Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shamim Sahranavard
- Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Astireh Salehi
- Biology Department, Islamic Azad University, Sanandaj, Iran
| | - Vahid Bagheri
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
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30
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El-Zahed MM, Baka ZA, Abou-Dobara MI, El-Sayed AK, Aboser MM, Hyder A. In vivo toxicity and antitumor activity of newly green synthesized reduced graphene oxide/silver nanocomposites. BIORESOUR BIOPROCESS 2021; 8:44. [PMID: 38650286 PMCID: PMC10992821 DOI: 10.1186/s40643-021-00400-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 05/30/2021] [Indexed: 02/07/2023] Open
Abstract
A novel biosynthesis of dual reduced graphene oxide/silver nanocomposites (rGO/AgNC) using the crude metabolite of Escherichia coli D8 (MF06257) strain and sunlight is introduced in this work. Physicochemical analysis of these rGO/AgNC revealed that they are sheet-like structures having spherically shaped silver nanoparticles (AgNPs) with an average particle size of 8 to 17 nm, and their absorption peak ranged from 350 to 450 nm. The biosynthesized rGO/AgNC were characterized by UV-vis and FT-IR spectra, X-ray diffraction, Zeta potential and transmission electron microscopy. After the injection of these nanocomposites to mice, their uptake by the kidney and liver has been proven by the ultrastructural observation and estimation of the hepatic and renal silver content. These nanocomposites caused a moderate toxicity for both organs. Changes in the liver and kidney functions and histopathological effects had been observed. The rGO/AgNC revealed a remarkable antitumor effect. They showed a dose-dependent cytotoxic effect on Ehrlich ascites carcinoma (EAC) cells in vitro. Treatment of mice bearing EAC tumors intraperitoneally with 10 mg/kg rGO/AgNC showed an antiproliferative effect on EAC cells, reduced ascites volume, and maintained mice survival. The results indicate that this green synergy of silver nanoparticles with reduced graphene oxide may have a promising potential in cancer therapy.
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Affiliation(s)
- Mohamed M El-Zahed
- Department of Botany and Microbiology, Faculty of Science, Damietta University, New Damietta, 34517, Egypt.
| | - Zakaria A Baka
- Department of Botany and Microbiology, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
| | - Mohamed I Abou-Dobara
- Department of Botany and Microbiology, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
| | - Ahmed K El-Sayed
- Department of Botany and Microbiology, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
| | - Magy M Aboser
- Department of Chemistry, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
| | - Ayman Hyder
- Department of Zoology, Faculty of Science, Damietta University, New Damietta, 34517, Egypt
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31
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Chen C, Lv Y. The biological behavior of drug-resistantovarian cancer cells and changes in the CA125 and HE4 levels after CIK interventions. Am J Transl Res 2021; 13:2976-2982. [PMID: 34017464 PMCID: PMC8129276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 12/24/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVE This study aimed to investigate the biological behavior of drug-resistant ovarian cancer cells and changes in the cancer antigen 125 (CA125) and human epididymal protein 4 (HE4) levels after the application of cytokine-induced killer (CIK) intervention. METHODS Drug-resistant ovarian cancer cells (namely SKVCR) were treated with CIK at different concentrations to observe the changes in the cell survival and cell morphology and the CA125, HE4, cytokine transforming growth factor-α (TGF-α), and tumor necrosis factor-α (TNF-α) levels in the cell lines before and after intervention. RESULTS With an increase in the CIK concentration, the survival rate of the SKVCR cell lines showed a decreasing trend. Under a constant CIK concentration, the survival rate of the SKVCR cell lines gradually decreased over time but become stable at 72 h. Before the CIK intervention, the SKVCR cells were full and rounded in shape, but after the CIK intervention, there was remarkable cell shrinkage and an increase in apoptotic cells. Compared with before the CIK intervention, the CA125 and HE4 levels were significantly decreased, but the TGF-α and TNF-α levels were increased (P<0.05). CONCLUSION After the CIK intervention in the drug-resistant ovarian cancer cells, the cell survival rate decreases with an increase in the CIK concentration or an extension of the intervention time, and the cell morphology will be significantly improved, and the CA125, HE4, and other related cytokine levels will also change significantly, suggesting that CIK can kill drug-resistant ovarian cancer cells.
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Affiliation(s)
- Chenchen Chen
- Department of Gynecology, Affiliated Hospital of Jining Medical University Jining 272000, Shandong Province, China
| | - Yanhua Lv
- Department of Gynecology, Affiliated Hospital of Jining Medical University Jining 272000, Shandong Province, China
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32
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Gurunathan S, Kang MH, Jeyaraj M, Kim JH. Palladium Nanoparticle-Induced Oxidative Stress, Endoplasmic Reticulum Stress, Apoptosis, and Immunomodulation Enhance the Biogenesis and Release of Exosome in Human Leukemia Monocytic Cells (THP-1). Int J Nanomedicine 2021; 16:2849-2877. [PMID: 33883895 PMCID: PMC8055296 DOI: 10.2147/ijn.s305269] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Accepted: 03/11/2021] [Indexed: 12/23/2022] Open
Abstract
Background Exosomes are endosome-derived nano-sized vesicles that have emerged as important mediators of intercellular communication and play significant roles in various diseases. However, their applications are rigorously restricted by the limited secretion competence of cells. Therefore, strategies to enhance the production and functions of exosomes are warranted. Studies have shown that nanomaterials can significantly enhance the effects of cells and exosomes in intercellular communication; however, how palladium nanoparticles (PdNPs) enhance exosome release in human leukemia monocytic cells (THP-1) remains unclear. Therefore, this study aimed to address the effect of PdNPs on exosome biogenesis and release in THP-1 cells. Methods Exosomes were isolated by ultracentrifugation and ExoQuickTM and characterized by dynamic light scattering, nanoparticle tracking analysis system, scanning electron microscopy, transmission electron microscopy, EXOCETTM assay, and fluorescence polarization. The expression levels of exosome markers were analyzed via quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Results PdNP treatment enhanced the biogenesis and release of exosomes by inducing oxidative stress, endoplasmic reticulum stress, apoptosis, and immunomodulation. The exosomes were spherical in shape and had an average diameter of 50–80 nm. Exosome production was confirmed via total protein concentration, exosome counts, acetylcholinesterase activity, and neutral sphingomyelinase activity. The expression levels of TSG101, CD9, CD63, and CD81 were significantly higher in PdNP-treated cells than in control cells. Further, cytokine and chemokine levels were significantly higher in exosomes isolated from PdNP-treated THP-1 cells than in those isolated from control cells. THP-1 cells pre-treated with N-acetylcysteine or GW4869 showed significant decreases in PdNP-induced exosome biogenesis and release. Conclusion To our knowledge, this is the first study showing that PdNPs stimulate exosome biogenesis and release and simultaneously increase the levels of cytokines and chemokines by modulating various physiological processes. Our findings suggest a reasonable approach to improve the production of exosomes for various therapeutic applications.
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Affiliation(s)
| | - Min-Hee Kang
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, Korea
| | - Muniyandi Jeyaraj
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, Korea
| | - Jin-Hoi Kim
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul, Korea
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33
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Parvanak Boroujeni K, Tohidiyan Z, Lorigooini Z, Hamidifar Z, Eskandari MM. Co-Sn-Cu oxides/graphene nanocomposites as green catalysts for preparing 1,8-dioxo-octahydroxanthenes and apoptosis-inducing agents in MCF-7 human breast cancer cells. IET Nanobiotechnol 2021; 15:197-211. [PMID: 34694698 PMCID: PMC8675816 DOI: 10.1049/nbt2.12006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 07/26/2020] [Accepted: 08/17/2020] [Indexed: 11/19/2022] Open
Abstract
In this work, Co-Sn-Cu oxides/graphene nanocomposite, 30-40 ± 0.5 nm in size, was synthesized by solid-state microwave irradiation. This method presents several advantages such as operational simplicity, fast, low cost, safe and energy efficient, and suitability for production of high purity of nanoparticles. Other advantages of this method are there is no need for the use of solvent, fuel, and surfactant. Co-Sn-Cu oxides/graphene nanocomposites have been characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometer, energy-dispersive X-ray spectroscopy, and UV-Vis spectroscopy. The synthesized nanocomposites were used as novel highly efficient catalysts for the synthesis of 1,8-dioxo-octahydroxanthenes at room temperature. The catalysts are recoverable and can be reused for six runs without loss of their activity. Also, the obtained nanocomposites exhibited significant anticancer activity against breast cancer cells and they could induce apoptosis in cancer cells.
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Affiliation(s)
| | - Zeinab Tohidiyan
- Department of ChemistryShahrekord BranchIslamic Azad UniversityShahrekordIran
| | - Zahra Lorigooini
- Medical Plants Research CenterBasic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran
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34
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Raja IS, Vedhanayagam M, Preeth DR, Kim C, Lee JH, Han DW. Development of Two-Dimensional Nanomaterials Based Electrochemical Biosensors on Enhancing the Analysis of Food Toxicants. Int J Mol Sci 2021; 22:3277. [PMID: 33806998 PMCID: PMC8005143 DOI: 10.3390/ijms22063277] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 03/19/2021] [Accepted: 03/21/2021] [Indexed: 12/25/2022] Open
Abstract
In recent times, food safety has become a topic of debate as the foodborne diseases triggered by chemical and biological contaminants affect human health and the food industry's profits. Though conventional analytical instrumentation-based food sensors are available, the consumers did not appreciate them because of the drawbacks of complexity, greater number of analysis steps, expensive enzymes, and lack of portability. Hence, designing easy-to-use tests for the rapid analysis of food contaminants has become essential in the food industry. Under this context, electrochemical biosensors have received attention among researchers as they bear the advantages of operational simplicity, portability, stability, easy miniaturization, and low cost. Two-dimensional (2D) nanomaterials have a larger surface area to volume compared to other dimensional nanomaterials. Hence, researchers nowadays are inclined to develop 2D nanomaterials-based electrochemical biosensors to significantly improve the sensor's sensitivity, selectivity, and reproducibility while measuring the food toxicants. In the present review, we compile the contribution of 2D nanomaterials in electrochemical biosensors to test the food toxicants and discuss the future directions in the field. Further, we describe the types of food toxicity, methodologies quantifying food analytes, how the electrochemical food sensor works, and the general biomedical properties of 2D nanomaterials.
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Affiliation(s)
| | | | - Desingh Raj Preeth
- Chemical Biology and Nanobiotechnology Laboratory, AU-KBC Research Centre, Anna University, MIT Campus, Chromepet, Chennai 600 044, India;
| | - Chuntae Kim
- BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, Korea; (I.S.R.); (C.K.)
| | - Jong Hun Lee
- Department of Food Science and Biotechnology, Gachon University, Seongnam 13120, Korea
| | - Dong Wook Han
- BIO-IT Foundry Technology Institute, Pusan National University, Busan 46241, Korea; (I.S.R.); (C.K.)
- Department of Cogno-Mechatronics Engineering, College of Nanoscience & Nanotechnology, Pusan National University, Busan 46241, Korea
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Yuan YG, Cai HQ, Wang JL, Mesalam A, Md Talimur Reza AM, Li L, Chen L, Qian C. Graphene Oxide-Silver Nanoparticle Nanocomposites Induce Oxidative Stress and Aberrant Methylation in Caprine Fetal Fibroblast Cells. Cells 2021; 10:cells10030682. [PMID: 33808775 PMCID: PMC8003532 DOI: 10.3390/cells10030682] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/03/2021] [Accepted: 03/16/2021] [Indexed: 02/07/2023] Open
Abstract
Graphene oxide–silver nanoparticle (GO-AgNPs) nanocomposites have drawn much attention for their potential in biomedical uses. However, the potential toxicity of GO-AgNPs in animals and humans remains unknown, particularly in the developing fetus. Here, we reported the GO-AgNP-mediated cytotoxicity and epigenetic alteration status in caprine fetal fibroblast cells (CFFCs). In brief, the proliferation and apoptosis rate of GO-AgNP-treated CFFCs (4 and 8 µg/mL of GO-AgNPs) were measured using the cell-counting kit (CCK-8) assay and the annexin V/propidium iodide (PI) assay, respectively. In addition, the oxidative stress induced by GO-AgNPs and detailed mechanisms were studied by evaluating the generation of reactive oxygen species (ROS), superoxide dismutase (SOD), lactate dehydrogenase (LDH), malondialdehyde (MDA), and caspase-3 and abnormal methylation. The expression of pro- and anti-apoptotic genes and DNA methyltransferases was measured using reverse transcription followed by RT-qPCR. Our data indicated that GO-AgNPs cause cytotoxicity in a dose-dependent manner. GO-AgNPs induced significant cytotoxicity by the loss of cell viability, production of ROS, increasing leakage of LDH and level of MDA, increasing expression of pro-apoptotic genes, and decreasing expression of anti-apoptotic genes. GO-AgNPs incited DNA hypomethylation and the decreased expression of DNMT3A. Taken together, this study showed that GO-AgNPs increase the generation of ROS and cause apoptosis and DNA hypomethylation in CFFCs. Therefore, the potential applications of GO-AgNPs in biomedicine should be re-evaluated.
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Affiliation(s)
- Yu-Guo Yuan
- College of Veterinary Medicine/Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China; (H.-Q.C.); (J.-L.W.); (L.L.); (L.C.); (C.Q.)
- Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses/Jiangsu Key Laboratory of Zoonosis, Yangzhou 225009, China
- Correspondence: ; Tel.: +86-514-87979228
| | - He-Qing Cai
- College of Veterinary Medicine/Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China; (H.-Q.C.); (J.-L.W.); (L.L.); (L.C.); (C.Q.)
| | - Jia-Lin Wang
- College of Veterinary Medicine/Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China; (H.-Q.C.); (J.-L.W.); (L.L.); (L.C.); (C.Q.)
| | - Ayman Mesalam
- Department of Theriogenology, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt;
| | - Abu Musa Md Talimur Reza
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland;
| | - Ling Li
- College of Veterinary Medicine/Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China; (H.-Q.C.); (J.-L.W.); (L.L.); (L.C.); (C.Q.)
| | - Li Chen
- College of Veterinary Medicine/Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China; (H.-Q.C.); (J.-L.W.); (L.L.); (L.C.); (C.Q.)
| | - Chen Qian
- College of Veterinary Medicine/Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou 225009, China; (H.-Q.C.); (J.-L.W.); (L.L.); (L.C.); (C.Q.)
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Chowdhury S, Ghosh S. Nanoparticles and Stem Cells. Stem Cells 2021. [DOI: 10.1007/978-981-16-1638-9_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Kharkar PS. Cancer Stem Cell (CSC) Inhibitors in Oncology-A Promise for a Better Therapeutic Outcome: State of the Art and Future Perspectives. J Med Chem 2020; 63:15279-15307. [PMID: 33325699 DOI: 10.1021/acs.jmedchem.0c01336] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Cancer stem cells (CSCs), a subpopulation of cancer cells endowed with self-renewal, tumorigenicity, pluripotency, chemoresistance, differentiation, invasive ability, and plasticity, reside in specialized tumor niches and are responsible for tumor maintenance, metastasis, therapy resistance, and tumor relapse. The new-age "hierarchical or CSC" model of tumor heterogeneity is based on the concept of eradicating CSCs to prevent tumor relapse and therapy resistance. Small-molecular entities and biologics acting on various stemness signaling pathways, surface markers, efflux transporters, or components of complex tumor microenvironment are under intense investigation as potential anti-CSC agents. In addition, smart nanotherapeutic tools have proved their utility in achieving CSC targeting. Several CSC inhibitors in clinical development have shown promise, either as mono- or combination therapy, in refractory and difficult-to-treat cancers. Clinical investigations with CSC marker follow-up as a measure of clinical efficacy are needed to turn the "hype" into the "hope" these new-age oncology therapeutics have to offer.
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Affiliation(s)
- Prashant S Kharkar
- Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400 019, India
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Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer. Int J Mol Sci 2020; 21:ijms21186792. [PMID: 32947930 PMCID: PMC7554966 DOI: 10.3390/ijms21186792] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 09/09/2020] [Accepted: 09/11/2020] [Indexed: 12/13/2022] Open
Abstract
Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.
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Liu L, Zhang M, Zhang Q, Jiang W. Graphene nanosheets damage the lysosomal and mitochondrial membranes and induce the apoptosis of RBL-2H3 cells. THE SCIENCE OF THE TOTAL ENVIRONMENT 2020; 734:139229. [PMID: 32450398 DOI: 10.1016/j.scitotenv.2020.139229] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 04/27/2020] [Accepted: 05/03/2020] [Indexed: 06/11/2023]
Abstract
The induced membrane damage is a key mechanism for the cytotoxicity of graphene nanosheets (GNSs). In this research, the physical interaction of GNSs on model membranes was investigated using artificial membranes and plasma membrane vesicles. The effects of the GNSs on plasma membrane, lysosomal and mitochondrial membranes were investigated using rat basophilic leukemia (RBL2H3) cells via lactate dehydrogenase (LDH) assay, acridine orange staining and JC-1 probe, respectively. The physical interaction with model membranes was dominated by electrostatic forces, and the adhered GNSs disrupted the membrane. The degree of physical membrane disruption was quantified by the quartz crystal microbalance with dissipation (QCM-D), confirming the serious membrane disruption. The internalized GNSs were mainly distributed in the lysosomes. They caused plasma membrane leakage, increased the lysosomal membrane permeability (LMP), and depolarized the mitochondrial membrane potential (MMP). The increased cellular levels of reactive oxygen species (ROS) were also detected after GNS exposure. The combination of physical interaction and the excess ROS production damaged the plasma and organelle membranes in living RBL-2H3 cells. The lysosomal and mitochondrial dysfunction, and the oxidative stress further induced cell apoptosis. Specially, the exposure to 25 mg/L GNSs caused severest cell mortality, plasma membrane damage, ROS generation, MMP depolarization and apoptosis. The research findings provide more comprehensive information on the graphene-induced plasma and organelle membrane damage, which is important to understand and predict the cytotoxicity of carbon-based nanomaterials.
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Affiliation(s)
- Ling Liu
- Environment Research Institute, Shandong University, Qingdao 266237, China
| | - Mengmeng Zhang
- Environment Research Institute, Shandong University, Qingdao 266237, China
| | - Qiu Zhang
- School of Environmental Sciences and Engineering, Shandong University, Qingdao 266237, China
| | - Wei Jiang
- Environment Research Institute, Shandong University, Qingdao 266237, China; Shenzhen Research Institute, Shandong University, Shenzhen 518057, China.
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Li N, Zhan X. MASS SPECTROMETRY-BASED MITOCHONDRIAL PROTEOMICS IN HUMAN OVARIAN CANCERS. MASS SPECTROMETRY REVIEWS 2020; 39:471-498. [PMID: 32020673 DOI: 10.1002/mas.21618] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Accepted: 01/22/2020] [Indexed: 06/10/2023]
Abstract
The prominent characteristics of mitochondria are highly dynamic and regulatory, which have crucial roles in cell metabolism, biosynthetic, senescence, apoptosis, and signaling pathways. Mitochondrial dysfunction might lead to multiple serious diseases, including cancer. Therefore, identification of mitochondrial proteins in cancer could provide a global view of tumorigenesis and progression. Mass spectrometry-based quantitative mitochondrial proteomics fulfils this task by enabling systems-wide, accurate, and quantitative analysis of mitochondrial protein abundance, and mitochondrial protein posttranslational modifications (PTMs). Multiple quantitative proteomics techniques, including isotope-coded affinity tag, stable isotope labeling with amino acids in cell culture, isobaric tags for relative and absolute quantification, tandem mass tags, and label-free quantification, in combination with different PTM-peptide enrichment methods such as TiO2 enrichment of tryptic phosphopeptides and antibody enrichment of other PTM-peptides, increase flexibility for researchers to study mitochondrial proteomes. This article reviews isolation and purification of mitochondria, quantitative mitochondrial proteomics, quantitative mitochondrial phosphoproteomics, mitochondrial protein-involved signaling pathway networks, mitochondrial phosphoprotein-involved signaling pathway networks, integration of mitochondrial proteomic and phosphoproteomic data with whole tissue proteomic and transcriptomic data and clinical information in ovarian cancers (OC) to in-depth understand its molecular mechanisms, and discover effective mitochondrial biomarkers and therapeutic targets for predictive, preventive, and personalized treatment of OC. This proof-of-principle model about OC mitochondrial proteomics is easily implementable to other cancer types. © 2020 John Wiley & Sons Ltd. Mass Spec Rev.
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Affiliation(s)
- Na Li
- University Creative Research Initiatives Center, Shandong First Medical University, Shandong, 250062, P. R. China
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P. R. China
- State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P. R. China
| | - Xianquan Zhan
- University Creative Research Initiatives Center, Shandong First Medical University, Shandong, 250062, P. R. China
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P. R. China
- State Local Joint Engineering Laboratory for Anticancer Drugs, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, 410008, P. R. China
- Department of Oncology, Xiangya Hospital, Central South University, 88 Xiangya Road, Changsha, Hunan, 410008, P. R. China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, 88 Xiangya Road, Changsha, Hunan, 410008, P. R. China
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Graphene-based multifunctional nanosystems for simultaneous detection and treatment of breast cancer. Colloids Surf B Biointerfaces 2020; 193:111104. [DOI: 10.1016/j.colsurfb.2020.111104] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 04/05/2020] [Accepted: 04/29/2020] [Indexed: 12/19/2022]
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Barrera CC, Groot H, Vargas WL, Narváez DM. Efficacy and Molecular Effects of a Reduced Graphene Oxide/Fe 3O 4 Nanocomposite in Photothermal Therapy Against Cancer. Int J Nanomedicine 2020; 15:6421-6432. [PMID: 32922009 PMCID: PMC7457756 DOI: 10.2147/ijn.s256760] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Accepted: 07/19/2020] [Indexed: 12/17/2022] Open
Abstract
PURPOSE Expanded research on the biomedical applications of graphene has shown promising results, although interactions between cells and graphene are still unclear. The current study aims to dissect the cellular and molecular effects of graphene nanocomposite in photothermal therapy against cancer, and to evaluate its efficacy. METHODS In this study, a reduced graphene oxide and iron oxide (rGO-Fe3O4) nanocomposite was obtained by chemical synthesis. The nanocomposite was fully characterized by Raman spectroscopy, TEM, VSM and thermal profiling. Cell-nanocomposite interaction was evaluated by confocal microscopy and viability assays on cancer cell line HeLa. The efficacy of the thermal therapy and changes in gene expression of Bcl-2 and Hsp70 was assessed. RESULTS The resulting rGO-Fe3O4 nanocomposite exhibited superparamagnetic properties and the capacity to increase the surrounding temperature by 18-20°C with respect to the initial temperature. The studies of cell-nanocomposite interaction showed that rGO-Fe3O4 attaches to cell membrane but there is a range of concentration at which the nanomaterial preserves cell viability. Photothermal therapy reduced cell viability to 32.6% and 23.7% with 50 and 100 µg/mL of nanomaterial, respectively. The effect of treatment on the molecular mechanism of cell death demonstrated an overexpression of anti-apoptotic proteins Hsp70 and Bcl-2 as an initial response to the therapy and depending on the aggressiveness of the treatment. CONCLUSION The results of this study contribute to understanding the interactions between cell and graphene and support its application in photothermal therapy against cancer due to its promising results.
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Affiliation(s)
- Claudia C Barrera
- Human Genetics Laboratory, Department of Biological Sciences, Universidad de Los Andes, Bogotá, Colombia
| | - Helena Groot
- Human Genetics Laboratory, Department of Biological Sciences, Universidad de Los Andes, Bogotá, Colombia
| | - Watson L Vargas
- Department of Chemical Engineering, Universidad de Los Andes, Bogotá, Colombia
| | - Diana M Narváez
- Human Genetics Laboratory, Department of Biological Sciences, Universidad de Los Andes, Bogotá, Colombia
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Zuber E, Schweitzer D, Allen D, Parte S, Kakar SS. Stem Cells in Ovarian Cancer and Potential Therapies. PROCEEDINGS OF STEM CELL RESEARCH AND ONCOGENESIS 2020; 8:e1001. [PMID: 32776013 PMCID: PMC7413600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Affiliation(s)
- Elena Zuber
- Department of Physiology, University of Louisville, Louisville, KY40202
| | - Diana Schweitzer
- Department of Physiology, University of Louisville, Louisville, KY40202
| | - Dominick Allen
- Department of Physiology, University of Louisville, Louisville, KY40202
| | - Seema Parte
- Department of Biochemistry and Molecular Biology, University of Nebraska, Omaha, NE-68198-5870
| | - Sham S. Kakar
- Department of Physiology, University of Louisville, Louisville, KY40202
- James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202
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Gurunathan S, Jeyaraj M, Kang MH, Kim JH. Melatonin Enhances Palladium-Nanoparticle-Induced Cytotoxicity and Apoptosis in Human Lung Epithelial Adenocarcinoma Cells A549 and H1229. Antioxidants (Basel) 2020; 9:E357. [PMID: 32344592 PMCID: PMC7222421 DOI: 10.3390/antiox9040357] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/18/2020] [Accepted: 04/22/2020] [Indexed: 02/07/2023] Open
Abstract
Palladium nanoparticles (PdNPs) are increasingly being used in medical and biological applications due to their unique physical and chemical properties. Recent evidence suggests that these nanoparticles can act as both a pro-oxidant and as an antioxidant. Melatonin (MLT), which also shows pro- and antioxidant properties, can enhance the efficacy of chemotherapeutic agents when combined with anticancer drugs. Nevertheless, studies regarding the molecular mechanisms underlying the anticancer effects of PdNPs and MLT in cancer cells are still lacking. Therefore, we aimed to investigate the potential toxicological and molecular mechanisms of PdNPs, MLT, and the combination of PdNPs with MLT in A549 lung epithelial adenocarcinoma cells. We evaluated cell viability, cell proliferation, cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis in cells treated with different concentrations of PdNPs and MLT. PdNPs and MLT induced cytotoxicity, which was confirmed by leakage of lactate dehydrogenase, increased intracellular protease, and reduced membrane integrity. Oxidative stress increased the levels of reactive oxygen species (ROS), malondialdehyde (MDA), nitric oxide (NO), protein carbonyl content (PCC), lipid hydroperoxide (LHP), and 8-isoprostane. Combining PdNPs with MLT elevated the levels of mitochondrial dysfunction by decreasing mitochondrial membrane potential (MMP), ATP content, mitochondrial number, and expression levels of the main regulators of mitochondrial biogenesis. Additionally, PdNPs and MLT induced apoptosis and oxidative DNA damage due to accumulation of 4-hydroxynonenal (HNE), 8-oxo-2'-deoxyguanosine (8-OhdG), and 8-hydroxyguanosine (8-OHG). Finally, PdNPs and MLT increased mitochondrially mediated stress and apoptosis, which was confirmed by the increased expression levels of apoptotic genes. To our knowledge, this is the first study demonstrating the effects of combining PdNPs and MLT in human lung cancer cells. These findings provide valuable insights into the molecular mechanisms involved in PdNP- and MLT-induced toxicity, and it may be that this combination therapy could be a potential effective therapeutic approach. This combination effect provides information to support the clinical evaluation of PdNPs and MLT as a suitable agents for lung cancer treatment, and the combined effect provides therapeutic value, as non-toxic concentrations of PdNPs and MLT are more effective, better tolerated, and show less adverse effects. Finally, this study suggests that MLT could be used as a supplement in nano-mediated combination therapies used to treat lung cancer.
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Affiliation(s)
- Sangiliyandi Gurunathan
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea; (M.J.); (M.-H.K.)
| | | | | | - Jin-Hoi Kim
- Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea; (M.J.); (M.-H.K.)
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Safety assessment control on mouse fibroblast cells compared with various chemically synthesized graphene oxide nanocomposites. CHEMICAL PAPERS 2020. [DOI: 10.1007/s11696-020-01133-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Current Use of Carbon-Based Materials for Biomedical Applications—A Prospective and Review. Processes (Basel) 2020. [DOI: 10.3390/pr8030355] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Among a large number of current biomedical applications in the use of medical devices, carbon-based nanomaterials such as graphene (G), graphene oxides (GO), reduced graphene oxide (rGO), and carbon nanotube (CNT) are frontline materials that are suitable for developing medical devices. Carbon Based Nanomaterials (CBNs) are becoming promising materials due to the existence of both inorganic semiconducting properties and organic π-π stacking characteristics. Hence, it could effectively simultaneously interact with biomolecules and response to the light. By taking advantage of such aspects in a single entity, CBNs could be used for developing biomedical applications in the future. The recent studies in developing carbon-based nanomaterials and its applications in targeting drug delivery, cancer therapy, and biosensors. The development of conjugated and modified carbon-based nanomaterials contributes to positive outcomes in various therapies and achieved emerging challenges in preclinical biomedical applications. Subsequently, diverse biomedical applications of carbon nanotube were also deliberately discussed in the light of various therapeutic advantages.
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Cobos M, De-La-Pinta I, Quindós G, Fernández MJ, Fernández MD. Graphene Oxide-Silver Nanoparticle Nanohybrids: Synthesis, Characterization, and Antimicrobial Properties. NANOMATERIALS (BASEL, SWITZERLAND) 2020; 10:E376. [PMID: 32098083 PMCID: PMC7075288 DOI: 10.3390/nano10020376] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/17/2020] [Accepted: 02/19/2020] [Indexed: 12/12/2022]
Abstract
Drug resistance of pathogenic microorganisms has become a global public health problem, which has prompted the development of new materials with antimicrobial properties. In this context, antimicrobial nanohybrids are an alternative due to their synergistic properties. In this study, we used an environmentally friendly one-step approach to synthesize graphene oxide (GO) decorated with silver nanoparticles (GO-AgNPs). By this process, spherical AgNPs of average size less than 4 nm homogeneously distributed on the surface of the partially reduced GO can be generated in the absence of any stabilizing agent, only with ascorbic acid (L-AA) as a reducing agent and AgNO3 as a metal precursor. The size of the AgNPs can be controlled by the AgNO3 concentration and temperature. Smaller AgNPs are obtained at lower concentrations of the silver precursor and lower temperatures. The antimicrobial properties of nanohybrids against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, Gram-positive Staphylococcus aureus, and the yeast Candida albicans were found to be concentration- and time-dependent. C. albicans and S. aureus showed the highest susceptibility to GO-AgNPs. These nanohybrids can be used as nanofillers in polymer nanocomposites to develop materials with antimicrobial activity for applications in different areas, and another potential application could be cancer therapeutic agents.
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Affiliation(s)
- Mónica Cobos
- Department of Polymer Science and Technology, Faculty of Chemistry, University of the Basque Country (UPV/EHU), Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain; (M.C.); (M.J.F.)
| | - Iker De-La-Pinta
- Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa 48940, Spain; (I.D.-L.-P.); (G.Q.)
| | - Guillermo Quindós
- Department of Immunology, Microbiology and Parasitology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena s/n, Leioa 48940, Spain; (I.D.-L.-P.); (G.Q.)
| | - M. Jesús Fernández
- Department of Polymer Science and Technology, Faculty of Chemistry, University of the Basque Country (UPV/EHU), Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain; (M.C.); (M.J.F.)
| | - M. Dolores Fernández
- Department of Polymer Science and Technology, Faculty of Chemistry, University of the Basque Country (UPV/EHU), Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain; (M.C.); (M.J.F.)
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Investigation of Cytotoxicity, Apoptosis, and Oxidative Stress Response of Fe 3O 4-RGO Nanocomposites in Human Liver HepG2 cells. MATERIALS 2020; 13:ma13030660. [PMID: 32024252 PMCID: PMC7040707 DOI: 10.3390/ma13030660] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 01/29/2020] [Accepted: 01/31/2020] [Indexed: 12/16/2022]
Abstract
Iron oxide–reduced graphene oxide (Fe3O4-RGO) nanocomposites have attracted enormous interest in the biomedical field. However, studies on biological response of Fe3O4-RGO nanocomposites at the cellular and molecular level are scarce. This study was designed to synthesize, characterize, and explore the cytotoxicity of Fe3O4-RGO nanocomposites in human liver (HepG2) cells. Potential mechanisms of cytotoxicity of Fe3O4-RGO nanocomposites were further explored through oxidative stress. Prepared samples were characterized by UV-visible spectrophotometer, X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and energy dispersive spectroscopy. The results demonstrated that RGO induce dose-dependent cytotoxicity in HepG2 cells. However, Fe3O4-RGO nanocomposites were not toxic. We further noted that RGO induce apoptosis in HepG2 cells, as evidenced by mitochondrial membrane potential loss, higher caspase-3 enzyme activity, and cell cycle arrest. On the other hand, Fe3O4-RGO nanocomposites did not alter these apoptotic parameters. Moreover, we observed that RGO increases intracellular reactive oxygen species and hydrogen peroxide while decrease antioxidant glutathione. Again, Fe3O4-RGO nanocomposites did not exert oxidative stress. Altogether, we found that RGO significantly induced cytotoxicity, apoptosis and oxidative stress. However, Fe3O4-RGO nanocomposites showed good biocompatibility to HepG2 cells. This study warrants further research to investigate the biological response of Fe3O4-RGO nanocomposites at the gene and molecular level.
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Misra R, Kandoi S, Varadaraj S, Vijayalakshmi S, Nanda A, Verma RS. Nanotheranostics: A tactic for cancer stem cells prognosis and management. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2019.101457] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Hussain Z, Thu HE, Sohail M, Khan S. Hybridization and functionalization with biological macromolecules synergistically improve biomedical efficacy of silver nanoparticles: Reconceptualization of in-vitro, in-vivo and clinical studies. J Drug Deliv Sci Technol 2019. [DOI: 10.1016/j.jddst.2019.101169] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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