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Souiade L, Rodriguez-Garcia MR, Serrano-Olmedo JJ, Ramos-Gómez M. Pulsed Alternating Fields Magnetic Hyperthermia in Combination with Chemotherapy (5-Fluorouracil) as a Cancer Treatment for Glioblastoma Multiform: An In Vitro Study. NANOMATERIALS (BASEL, SWITZERLAND) 2025; 15:556. [PMID: 40214600 PMCID: PMC11990194 DOI: 10.3390/nano15070556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2025] [Revised: 03/25/2025] [Accepted: 04/02/2025] [Indexed: 04/14/2025]
Abstract
Inducing magnetic hyperthermia (MHT) involves locally raising the temperature to 39-45 °C, which increases the susceptibility of tumor cells to therapeutic agents without damaging healthy tissues. Recent studies on trapezoidal pulsed alternating magnetic fields (TP-AMFs) have proven their considerable efficacy in increasing the temperature of magnetic nanoparticles (MNPs) compared to sinusoidal fields. Thermal therapies have been known to incorporate multiple combinations of therapeutic approaches to optimize the medical procedure for healing cancer patients such as chemotherapy and radiotherapy. The combination of MHT with chemotherapy aims to enhance the therapeutic effects against cancer due to the synergistic interaction in tumor cells. In this study, we aim to exploit the synergistic effects of combining MHT produced by TP-AMFs with a low concentration of 5-Fluorouracil (5-FU) to optimize the therapeutic outcomes in comparison to TP-AMFs MHT alone. Hence, we exposed a glioblastoma cell line (CT2A) incubated with iron oxide nanoparticles at 1 mg/mL to two cycles of MHT employing a trapezoidal-square waveform at 200 kHz and 2 mT for 30 min for each cycle, separated by a 45 min break, both as a single treatment and in combination with 0.1 μg/mL of 5-FU. Our findings demonstrated the efficacy of the synergistic effect between MHT treatment via TP-AMFs and the 5-FU, increasing the cell death to 58.9 ± 2%, compared to 31.4 ± 3% with MHT treatment alone. Cell death was primarily driven by the necrosis pathway (47.3 ± 2%) compared to apoptosis (11.6 ± 2). The addition of 5-FU enhanced the cytotoxic effect of MHT on CT2A cells, increasing the calreticulin (CRT) positive cells to 17 ± 1% compared to 10 ± 1% as produced by MHT treatment alone. Furthermore, this combination suggests that the employed treatment approach can promote immune system activation due to the exposure of CRT in the treated cells.
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Affiliation(s)
- Lilia Souiade
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Pozuelo de Alarcón, 28223 Madrid, Spain; (L.S.); (M.-R.R.-G.); (J.-J.S.-O.)
| | - Miguel-Ramon Rodriguez-Garcia
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Pozuelo de Alarcón, 28223 Madrid, Spain; (L.S.); (M.-R.R.-G.); (J.-J.S.-O.)
| | - José-Javier Serrano-Olmedo
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Pozuelo de Alarcón, 28223 Madrid, Spain; (L.S.); (M.-R.R.-G.); (J.-J.S.-O.)
- Centro de Investigación Biomédica en Red para Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento de Tecnología Fotónica y Bioingeniería, ETSI Telecomunicaciones, Universidad Politécnica de Madrid, 28040 Madrid, Spain
| | - Milagros Ramos-Gómez
- Centro de Tecnología Biomédica, Universidad Politécnica de Madrid, Campus de Montegancedo, Pozuelo de Alarcón, 28223 Madrid, Spain; (L.S.); (M.-R.R.-G.); (J.-J.S.-O.)
- Centro de Investigación Biomédica en Red para Bioingeniería, Biomateriales y Nanomedicina, Instituto de Salud Carlos III, 28029 Madrid, Spain
- Departamento de Tecnología Fotónica y Bioingeniería, ETSI Telecomunicaciones, Universidad Politécnica de Madrid, 28040 Madrid, Spain
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Izadiyan Z, Misran M, Kalantari K, Webster TJ, Kia P, Basrowi NA, Rasouli E, Shameli K. Advancements in Liposomal Nanomedicines: Innovative Formulations, Therapeutic Applications, and Future Directions in Precision Medicine. Int J Nanomedicine 2025; 20:1213-1262. [PMID: 39911259 PMCID: PMC11794392 DOI: 10.2147/ijn.s488961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Accepted: 01/01/2025] [Indexed: 02/07/2025] Open
Abstract
Liposomal nanomedicines have emerged as a pivotal approach for the treatment of various diseases, notably cancer and infectious diseases. This manuscript provides an in-depth review of recent advancements in liposomal formulations, highlighting their composition, targeted delivery strategies, and mechanisms of action. We explore the evolution of liposomal products currently in clinical trials, emphasizing their potential in addressing diverse medical challenges. The integration of immunotherapeutic agents within liposomes marks a paradigm shift, enabling the design of 'immuno-modulatory hubs' capable of orchestrating precise immune responses while facilitating theranostic applications. The recent COVID-19 pandemic has accelerated research in liposomal-based vaccines and antiviral therapies, underscoring the need for improved delivery mechanisms to overcome challenges like rapid clearance and organ toxicity. Furthermore, we discuss the potential of "smart" liposomes, which can respond to specific disease microenvironments, enhancing treatment efficacy and precision. The integration of artificial intelligence and machine learning in optimizing liposomal designs promises to revolutionize personalized medicine, paving the way for innovative strategies in disease detection and therapeutic interventions. This comprehensive review underscores the significance of ongoing research in liposomal technologies, with implications for future clinical applications and enhanced patient outcomes.
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Affiliation(s)
- Zahra Izadiyan
- Department of Chemistry, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Misni Misran
- Department of Chemistry, Universiti Malaya, Kuala Lumpur, Malaysia
| | - Katayoon Kalantari
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Thomas J Webster
- Biomedical Engineering, Hebei University of Technology, Tianjin, People’s Republic of China
- School of Engineering, Saveetha University, Chennai, India
| | - Pooneh Kia
- Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
| | | | - Elisa Rasouli
- Department of Electrical and Electronics Engineering, Nanyang Technological University, Nanyang, Singapore
| | - Kamyar Shameli
- School of Medicine, Institute of Virology, Technical University of Munich, Munich, Germany
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da Costa E Silva RMF, Andrade ÂL, Freitas ETF, Valverde TM, Lara LRS, Martins DA, Lopez JL, Stumpf HO, Nascentes CC, de Goes AM, Domingues RZ. Formation and stability of green and low-cost magnetoliposomes of the soy lecithin, stigmasterol, and β-sitosterol for hyperthermia treatments. Sci Rep 2025; 15:2831. [PMID: 39843908 PMCID: PMC11754809 DOI: 10.1038/s41598-024-82480-x] [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: 06/02/2024] [Accepted: 12/04/2024] [Indexed: 01/24/2025] Open
Abstract
Magnetoliposomes containing magnetite, soy lecithin, stigmasterol, and beta-sitosterol of the mean size minor than 160 nm were obtained by a scalable and green process using autoclave and sonication without organic solvents. The formation, size of the liposome, linkage, and encapsulation of the magnetite were evaluated by Cryo-TEM. The stability of magnetoliposomes after storage for 6 months at 4 °C was improved by liposome size, the ability of soy lecithin to preserve the magnetite phase against oxidation, pH, polydispersity index, and zeta potential. The iron oxide phase stability was assessed using no conventional X-ray diffraction (high-resolution transmission electron microscopy), energy loss electron spectroscopy, and selected area electron diffraction) in time zero (fresh sample) and 6 months. The high zeta potential measured for magnetoliposomes, │53│ mV, indicated a low tendency to agglomerate. Lip-Fe3O4@lecithin with concentrations of 0.58 mg mL-1 of liposome showed high cell viability and are potential candidates for drug delivery and hyperthermia treatments in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays.
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Affiliation(s)
| | - Ângela Leão Andrade
- Depto de Química, ICEB, Universidade Federal de Ouro Preto, UFOP, Ouro Preto, MG, CEP 35400-000, Brazil
| | - Erico Tadeu Fraga Freitas
- Centro de Microscopia, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, MG, CEP 31.270-901, Brazil
| | - Thalita Marcolan Valverde
- Depto de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, MG, CEP 31.270-901, Brazil
| | - Luciano Roni Silva Lara
- Universidade Estadual de Mato Grosso do Sul, Dourados, MS, CEP 79.804-970, Brazil
- Depto de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, CEP 31.270-901, Brazil
| | - Darliane Aparecida Martins
- Instituto Federal de Educação, Ciência e Tecnologia do Sul de Minas, Campus Pouso Alegre, Av. Maria da Conceição Santos, 900 - Parque Real, Pouso Alegre, MG, CEP 37550-000, Brazil
| | - Jorge Luis Lopez
- Centro de Ciências Biológicas e da Natureza, Universidade Federal do Acre, UFAC, Rio Branco, AC, CEP 69.920-900, Brazil
| | - Humberto Osório Stumpf
- Depto de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, CEP 31.270-901, Brazil
| | | | - Alfredo Miranda de Goes
- Depto de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, UFMG, Belo Horizonte, MG, CEP 31.270-901, Brazil
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Muolokwu CE, Gothwal A, Kanekiyo T, Singh J. Synthesis and Characterization of Transferrin and Cell-Penetrating Peptide-Functionalized Liposomal Nanoparticles to Deliver Plasmid ApoE2 In Vitro and In Vivo in Mice. Mol Pharm 2025; 22:229-241. [PMID: 39665408 PMCID: PMC11888121 DOI: 10.1021/acs.molpharmaceut.4c00870] [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] [Indexed: 12/13/2024]
Abstract
Alzheimer's disease (AD) is a prevalent neurodegenerative condition characterized by the aggregation of amyloid-β plaques and neurofibrillary tangles in the brain, leading to synaptic dysfunction and neuronal degeneration. Recently, new treatment approaches involving drugs such as donanemab and lecanemab have been introduced for AD. However, these drug regimens have been associated with adverse effects, leading to the exploration of gene therapy as a potential treatment option. The apolipoprotein E (ApoE) isoforms (ApoE2, ApoE3, and ApoE4) play pivotal roles in AD pathology, with ApoE2 known for its protective effects against AD, making it a promising candidate for gene therapy interventions. However, delivering therapeutics across the blood-brain barrier (BBB) remains a crucial challenge in treating neurological disorders. Liposomes, lipid-based vesicles, are effective nanocarriers due to their ability to shield therapeutics from degradation, though they often lack specificity for brain delivery. To address this issue, liposomes were functionalized with cell-penetrating peptides such as penetratin (Pen), cingulin (Cgn), and a targeting ligand transferrin (Tf). This modification strategy aimed to enhance the delivery of therapeutic ApoE2 plasmids across the BBB to neurons, thereby increasing the level of ApoE2 protein expression. Experimental findings demonstrated that dual-functionalized liposomes (CgnTf and PenTf) exhibited higher cellular uptake, biodistribution, and transfection efficiency than single-functionalized (Pen, Cgn, or Tf) and nonfunctionalized liposomes. In vitro studies using primary neuronal cells, bEnd.3 cells, and primary astrocytes consistently supported these findings. Following a single dose treatment via tail vein administration in C57BL6/J mice, in vivo biodistribution results showed significantly higher biodistribution levels in the brain (∼12% ID/gram of tissue) for dual-functionalized liposomes. Notably, treatment with dual-functionalized liposomes resulted in a 2-fold increase in ApoE2 expression levels compared to baseline levels. These findings highlight the potential of dual-functionalized liposomes as an efficacious delivery system for ApoE2 gene therapy in AD, highlighting a promising strategy to address the disease's underlying mechanisms.
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Affiliation(s)
- Chinenye Edith Muolokwu
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health and Human Sciences, North Dakota State University, Fargo, ND 58108-6050, USA
| | - Avinash Gothwal
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health and Human Sciences, North Dakota State University, Fargo, ND 58108-6050, USA
| | - Takahisa Kanekiyo
- Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA
| | - Jagdish Singh
- Department of Pharmaceutical Sciences, School of Pharmacy, College of Health and Human Sciences, North Dakota State University, Fargo, ND 58108-6050, USA
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Shahsavari S, Rad MB, Hajiaghajani A, Rostami M, Hakimian F, Jafarzadeh S, Hasany M, Collingwood JF, Aliakbari F, Fouladiha H, Bardania H, Otzen DE, Morshedi D. Magnetoresponsive liposomes applications in nanomedicine: A comprehensive review. Biomed Pharmacother 2024; 181:117665. [PMID: 39541790 DOI: 10.1016/j.biopha.2024.117665] [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: 07/09/2024] [Revised: 11/03/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024] Open
Abstract
Safe and effective cancer therapy requires a suitable nanocarrier that can target particular sites, such as cancer cells, in a selective manner. With the tremendous growth in nanotechnology, liposomes, among various competing nanocarriers, have shown promising advances in cancer therapy. Magnetic nanoparticles and metal ions are wide-reaching candidates for conferring magnetic properties and for incorporation into liposomes. Combining liposomes with magnetic structures enables construction of magnetoresponsive liposomes, allowing stimuli-responsiveness to an alternating magnetic field, magnetic targeting, and tracking by magnetic resonance imaging, which could all occur in parallel. This review presents a comprehensive analysis of the practical advances and novel aspects of design, synthesis and engineering magnetoresponsive liposomes, emphasizing their diverse properties for various applications. Our work explores the innovative uses of these structures, extending beyond drug delivery to include smart contrast agents, cell labeling, biosensing, separation, and filtering. By comparing new findings with earlier studies, we showcase significant improvements in efficiency and uncover new potentials, setting a new benchmark for future research in the field of magnetoresponsive liposomes.
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Affiliation(s)
- Shayan Shahsavari
- Iran Nanotechnology Innovation Council, Nanoclub Elites Association, Tehran, Iran
| | - Mohammad Behnam Rad
- Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran
| | - Amirhossein Hajiaghajani
- School of Electrical Engineering, Iran University of Science and Technology, Tehran 1684613114, Iran
| | | | - Fatemeh Hakimian
- Department of Biophysics, Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran
| | - Sina Jafarzadeh
- Department of Energy Conversion and Storage, Technical University of Denmark, Anker Engelunds Vej, Lyngby 2800 Kgs, Denmark
| | - Masoud Hasany
- Department of Civil and Mechanical Engineering, Technical University of Denmark, Lyngby 2800 Kgs, Denmark
| | | | - Farhang Aliakbari
- National Institute of Genetic Engineering and Biotechnology, Shahrak-e Pajoohesh, km 15 Tehran - Karaj Highway, P.O.Box:14965/161, Tehran, Iran; Molecular Medicine Research Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada
| | - Hamideh Fouladiha
- Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran
| | - Hassan Bardania
- Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran.
| | - Daniel E Otzen
- Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, Aarhus C DK-8000, Denmark.
| | - Dina Morshedi
- National Institute of Genetic Engineering and Biotechnology, Shahrak-e Pajoohesh, km 15 Tehran - Karaj Highway, P.O.Box:14965/161, Tehran, Iran.
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Sia CS, Tey BT, Goh BH, Low LE. Controlled assembly of superparamagnetic iron oxide nanoparticle into nanoliposome for Pickering emulsion preparation. Colloids Surf B Biointerfaces 2024; 241:114051. [PMID: 38954935 DOI: 10.1016/j.colsurfb.2024.114051] [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: 03/13/2024] [Revised: 04/22/2024] [Accepted: 06/19/2024] [Indexed: 07/04/2024]
Abstract
There has been a surge in effort in the development of various solid nanoparticles as Pickering emulsion stabilizers in the past decades. Regardless, the exploration of stabilizers that simultaneously stabilize and deliver bioactive has been limited. For this, liposomes with amphiphilic nature have been introduced as Pickering emulsion stabilizers but these nano-sized vesicles lack targeting specificity. Therefore in this study, superparamagnetic iron oxide nanoparticles (SPION) encapsulated within liposomes (MLP) were used as Pickering emulsion stabilizers to prepare pH and magnetic-responsive Pickering emulsions. A stable MLP-stabilized Pickering emulsion formulation was established by varying the MLP pH, concentration, and oil loading during the emulsification process. The primary stabilization mechanism of the emulsion under pH variation was identified to be largely associated with the MLP phosphate group deprotonation. When subjected to sequential pH adjustment to imitate the gastrointestinal digestion pH environment, a recovery in Pickering emulsion integrity was observed as the pH changes from acidic to alkaline. By incorporating SPION, the Pickering emulsion can be guided to the targeted site under the influence of a magnetic field without compromising emulsion stability. Overall, the results demonstrated the potential of MLP-stabilized Pickering emulsion as a dual pH- and magnetic-responsive drug delivery carrier with the ability to co-encapsulate hydrophobic and hydrophilic bioactive.
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Affiliation(s)
- Chin Siew Sia
- Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia; Medical Engineering and Technology (MET) Hub, School of Engineering, Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia
| | - Beng Ti Tey
- Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia
| | - Bey-Hing Goh
- Sunway Biofunctional Molecules Discovery Centre (SBMDC), School of Medical and Life Sciences, Sunway University, Subang Jaya, Selangor, 47500, Malaysia; Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo 2007, NSW, Australia; Biofunctional Molecule Exploratory Research (BMEX) Group, School of Pharmacy, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia
| | - Liang Ee Low
- Department of Chemical Engineering, School of Engineering, Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia; Medical Engineering and Technology (MET) Hub, School of Engineering, Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia; Monash-Industry Plant Oils Research Laboratory (MIPO), Monash University Malaysia, Subang Jaya, Selangor, 47500, Malaysia.
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7
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Alrbyawi H. Stimuli-Responsive Liposomes of 5-Fluorouracil: Progressive Steps for Safe and Effective Treatment of Colorectal Cancer. Pharmaceutics 2024; 16:966. [PMID: 39065663 PMCID: PMC11280302 DOI: 10.3390/pharmaceutics16070966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/15/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
5-Fluorouracil (5-FU) has become one of the most widely employed antimetabolite chemotherapeutic agents in recent decades to treat various types of cancer. It is considered the standard first-line treatment for patients with metastatic colorectal cancer. Unfortunately, traditional chemotherapy with 5-FU presents many limitations, such as a short half-life, a low bioavailability, and a high cytotoxicity, affecting both tumor tissue and healthy tissue. In order to overcome the drawbacks of 5-FU and enhance its therapeutic effectiveness against colorectal cancer, many studies have focused on designing new delivery systems to successfully deliver 5-FU to tumor sites. Liposomes have gained attention as a well-accepted nanocarrier for several chemotherapeutic agents. These amphipathic spherical vesicles consist of one or more phospholipid bilayers, showing promise for the drug delivery of both hydrophobic and hydrophilic components in addition to distinctive properties, such as biodegradability, biocompatibility, a low toxicity, and non-immunogenicity. Recent progress in liposomes has mainly focused on chemical and structural modifications to specifically target and activate therapeutic actions against cancer within the proximity of tumors. This review provides a comprehensive overview of both internal-stimuli-responsive liposomes, such as those activated by enzymes or pH, and external-stimuli-responsive liposomes, such as those activated by the application of a magnetic field, light, or temperature variations, for the site-specific delivery of 5-FU in colorectal cancer therapy, along with the future perspectives of these smart-delivery liposomes in colorectal cancer. In addition, this review critically highlights recent innovations in the literature on various types of stimuli-responsive liposomal formulations designed to be applied either exogenously or endogenously and that have great potential in delivering 5-FU to colorectal cancer sites.
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Affiliation(s)
- Hamad Alrbyawi
- Department of Pharmaceutics and Pharmaceutical Industries, College of Pharmacy, Taibah University, Madinah 41477, Saudi Arabia
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M E Gaafar P, Farid RM, Hazzah HA, AbouKilila HY, Helmy MW, Abdallah OY. Magnetic Lipid-Based hybrid nanosystems: A combined stimuli- responsive nanocarriers for enriched chemotherapeutic potential of L-carnosine in induced breast Ehrlich ascites tumor model. Int J Pharm 2024; 655:124000. [PMID: 38493840 DOI: 10.1016/j.ijpharm.2024.124000] [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: 12/16/2023] [Revised: 02/26/2024] [Accepted: 03/12/2024] [Indexed: 03/19/2024]
Abstract
Magnetic Lipid-Based Hybrid Nanosystems (M-LCNPs) is a novel nanoplatform that can respond to magnetic stimulus and are designed for delivering L-carnosine (CN), a challenging dipeptide employed in the treatment of breast cancer. CN exhibits considerable water solubility and undergoes in-vivo degradation, hence restricting its application. Consequently, it is anticipated that the developed M-LCNPs will enhance the effectiveness of CN. To ensure the physical stability of MNPs, they were initially coated with a mixture of oleic acid and oleylamine before being included in pegylated liquid crystalline nanoparticles (PLCNPs). The proposed M-LCNPs exhibited promising in-vitro characteristics, notably a small particle size (143.5 nm ± 1.25) and a high zeta potential (-39.5 mV ± 1.54), together with superparamagnetic behavior. The in-vitro release profile exhibited a prolonged release pattern. The IC50 values of M-LCNPs were 1.57 and 1.59 times lower than these of the CN solution after 24 and 48 hours, respectively. Female BALB/C female mice with an induced breast cancer (Ehrlich Ascites tumor [EAT] model) were used to study the influence of an external magnetic field on the chemotherapeutic activity and toxicity of CN loaded in the developed M-LCNPs. Stimuli-responsive M-LCNPs exhibited no apparent systemic toxicity in addition to enhanced chemotherapeutic efficacy compared to nontargeted M-LCNPs and CN solution, as evidenced by a reduction of % tumor growth (11.7%), VEGF levels (22.95 pg/g tissue), and cyclin D1 levels (27.61 ng/g tissue), and an increase in caspase-3 level (28.9 ng/g tissue). Ultimately, the developed stimuli-responsive CN loaded M-LCNPs presented a promising nanoplatform for breast cancer therapy.
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Affiliation(s)
- Passent M E Gaafar
- Department of Pharmaceutics, Division of Pharmaceutical Sciences, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, Egypt.
| | - Ragwa M Farid
- Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt
| | - Heba A Hazzah
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - HussamElDin Y AbouKilila
- Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, Egypt
| | - Maged W Helmy
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Ossama Y Abdallah
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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9
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Ashique S, Garg A, Hussain A, Farid A, Kumar P, Taghizadeh‐Hesary F. Nanodelivery systems: An efficient and target-specific approach for drug-resistant cancers. Cancer Med 2023; 12:18797-18825. [PMID: 37668041 PMCID: PMC10557914 DOI: 10.1002/cam4.6502] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 08/16/2023] [Accepted: 08/25/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND Cancer treatment is still a global health challenge. Nowadays, chemotherapy is widely applied for treating cancer and reducing its burden. However, its application might be in accordance with various adverse effects by exposing the healthy tissues and multidrug resistance (MDR), leading to disease relapse or metastasis. In addition, due to tumor heterogeneity and the varied pharmacokinetic features of prescribed drugs, combination therapy has only shown modestly improved results in MDR malignancies. Nanotechnology has been explored as a potential tool for cancer treatment, due to the efficiency of nanoparticles to function as a vehicle for drug delivery. METHODS With this viewpoint, functionalized nanosystems have been investigated as a potential strategy to overcome drug resistance. RESULTS This approach aims to improve the efficacy of anticancer medicines while decreasing their associated side effects through a range of mechanisms, such as bypassing drug efflux, controlling drug release, and disrupting metabolism. This review discusses the MDR mechanisms contributing to therapeutic failure, the most cutting-edge approaches used in nanomedicine to create and assess nanocarriers, and designed nanomedicine to counteract MDR with emphasis on recent developments, their potential, and limitations. CONCLUSIONS Studies have shown that nanoparticle-mediated drug delivery confers distinct benefits over traditional pharmaceuticals, including improved biocompatibility, stability, permeability, retention effect, and targeting capabilities.
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Affiliation(s)
- Sumel Ashique
- Department of PharmaceuticsPandaveswar School of PharmacyPandaveswarIndia
| | - Ashish Garg
- Guru Ramdas Khalsa Institute of Science and Technology, PharmacyJabalpurIndia
| | - Afzal Hussain
- Department of Pharmaceutics, College of PharmacyKing Saud UniversityRiyadhSaudi Arabia
| | - Arshad Farid
- Gomal Center of Biochemistry and BiotechnologyGomal UniversityDera Ismail KhanPakistan
| | - Prashant Kumar
- Teerthanker Mahaveer College of PharmacyTeerthanker Mahaveer UniversityMoradabadIndia
- Department of Pharmaceutics, Amity Institute of PharmacyAmity University Madhya Pradesh (AUMP)GwaliorIndia
| | - Farzad Taghizadeh‐Hesary
- ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of MedicineIran University of Medical SciencesTehranIran
- Clinical Oncology DepartmentIran University of Medical SciencesTehranIran
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10
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Gago L, Quiñonero F, Perazzoli G, Melguizo C, Prados J, Ortiz R, Cabeza L. Nanomedicine and Hyperthermia for the Treatment of Gastrointestinal Cancer: A Systematic Review. Pharmaceutics 2023; 15:1958. [PMID: 37514144 PMCID: PMC10386177 DOI: 10.3390/pharmaceutics15071958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 07/08/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
The incidence of gastrointestinal cancers has increased in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, needing the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria (studies in the last 10 years where hyperthermia using alternative magnetic field is applied), a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs in combination with magnetic hyperthermia demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies.
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Affiliation(s)
- Lidia Gago
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Francisco Quiñonero
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Gloria Perazzoli
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Jose Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Raul Ortiz
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
| | - Laura Cabeza
- Institute of Biopathology and Regenerative Medicine (IBIMER), Center of Biomedical Research (CIBM), University of Granada, 18100 Granada, Spain
- Department of Anatomy and Embryology, Faculty of Medicine, University of Granada, 18071 Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), SAS-University of Granada, 18014 Granada, Spain
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Xia H, Zhu J, Men C, Wang A, Mao Q, Feng Y, Li J, Xu J, Cheng X, Shi H. Light-initiated aggregation of gold nanoparticles for synergistic chemo-photothermal tumor therapy. NANOSCALE ADVANCES 2023; 5:3053-3062. [PMID: 37260491 PMCID: PMC10228337 DOI: 10.1039/d3na00114h] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 04/24/2023] [Indexed: 06/02/2023]
Abstract
The combination of chemotherapy with photothermal therapy (PTT) has attracted extensive attention due to its excellent synergetic effect attributing to the fact that hyperthermia can effectively promote the tumor uptake of chemotherapeutic drugs. Herein, we propose a light-initiated gold nanoparticle (AuNP) aggregation boosting the uptake of chemotherapeutic drugs for enhanced chemo-photothermal tumor therapy. Novel light-responsive AuNPs (tm-AuNPs) were rationally designed and fabricated by conjugating both 2,5-diphenyltetrazole (Tz) and methacrylic acid (Ma) onto the surface of AuNPs with small size (∼20 nm). Upon the irradiation of 405 nm laser, AuNPs could be initiated to form aggregates specifically within tumors through the covalent cycloaddition reaction between Tz and Ma. Taking advantage of the controllable photothermal effect of Au aggregates under NIR excitation, improved enrichment of doxorubicin (DOX) in tumor tissues was realized, combined with PTT, resulting in outstanding synergetic anti-tumor efficacy in living mice. We thus believe that this light-initiated AuNP aggregation approach would offer a valuable and powerful tool for precisely synergistic chemo-photothermal tumor therapy.
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Affiliation(s)
- Huawei Xia
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Jinfeng Zhu
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
- Department of Experimental Medicine, TOR, University of Rome Tor Vergata Roma 00133 Italy
| | - Changhe Men
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Anna Wang
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Qiulian Mao
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Yali Feng
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Jiachen Li
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Jingwei Xu
- Department of Cardiothoracic Surgery, Suzhou Municipal Hospital Institution Suzhou 215002 P. R. China
| | - Xiaju Cheng
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
| | - Haibin Shi
- State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X) and Collaborative Innovation Centre of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University 199 Renai Road Suzhou 215123 China
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12
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Lado-Touriño I, Cerpa-Naranjo A. Coarse-Grained Molecular Dynamics of pH-Sensitive Lipids. Int J Mol Sci 2023; 24:ijms24054632. [PMID: 36902063 PMCID: PMC10003205 DOI: 10.3390/ijms24054632] [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: 01/20/2023] [Revised: 02/20/2023] [Accepted: 02/25/2023] [Indexed: 03/06/2023] Open
Abstract
pH-sensitive lipids represent a class of lipids that can be protonated and destabilized in acidic environments, as they become positively charged in response to low-pH conditions. They can be incorporated into lipidic nanoparticles such as liposomes, which are able to change their properties and allow specific drug delivery at the acidic conditions encountered in some pathological microenvironments. In this work, we used coarse-grained molecular-dynamic simulations to study the stability of neutral and charged lipid bilayers containing POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and various kinds of ISUCA ((F)2-(imidazol-1-yl)succinic acid)-derived lipids, which can act as pH-sensitive molecules. In order to explore such systems, we used a MARTINI-derived forcefield, previously parameterized using all-atom simulation results. We calculated the average area per lipid, the second-rank order parameter and the lipid diffusion coefficient of both lipid bilayers made of pure components and mixtures of lipids in different proportions, under neutral or acidic conditions. The results show that the use of ISUCA-derived lipids disturbs the lipid bilayer structure, with the effect being particularly marked under acidic conditions. Although more-in depth studies on these systems must be carried out, these initial results are encouraging and the lipids designed in this research could be a good basis for developing new pH-sensitive liposomes.
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Ashique S, Garg A, Singh V, Rai G, Mishra N, Soni ML, Kumar S, Madamsetty VS. Role of Block Copolymers in Colon Cancer. BLOCK CO-POLYMERIC NANOCARRIERS: DESIGN, CONCEPT, AND THERAPEUTIC APPLICATIONS 2023:181-209. [DOI: 10.1007/978-981-99-6917-3_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Garrós N, Mallandrich M, Beirampour N, Mohammadi R, Domènech Ò, Rodríguez-Lagunas MJ, Clares B, Colom H. Baricitinib Liposomes as a New Approach for the Treatment of Sjögren’s Syndrome. Pharmaceutics 2022; 14:pharmaceutics14091895. [PMID: 36145642 PMCID: PMC9505846 DOI: 10.3390/pharmaceutics14091895] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 08/25/2022] [Accepted: 09/04/2022] [Indexed: 12/05/2022] Open
Abstract
Sjögren’s syndrome is a chronic systemic autoimmune disease affecting from 0.2 to 3% of the general population. The current treatment for Sjögren’s syndrome is aimed at controlling symptoms such as dry eyes and xerostomia. Systemic therapy with glucocorticoids or immunosuppressants is also used. Baricitinib is an immunosuppressant drug, specifically a Janus kinases 1 and 2 selective inhibitor. We propose ocular liposomal formulations loaded with baricitinib for the management of Sjögren’s syndrome. The novelty of the work relies on the fact that, for the first time, baricitinib is intended to be used for topical delivery. Two liposomal formulations were prepared with different lipids: (i) L-α-phosphatidylcholine (Lα-PC) and (ii) a combination of lipids 1-palmitoyl-2-oleoyl-phosphatidylethanolamine: s1-Palmitoyl-2-oleoyl-sn-glycerol-3-phosphoglycerol (3:1, mol/mol) (POPE:POPG), and they were physicochemically characterized. The in vitro drug release and the ex vivo permeation through corneal and scleral tissues were also assessed. Finally, the tolerance of the formulations on the ocular tissues was evaluated by the HET-CAM technique, as well as through the histological analysis of the cornea and sclera and the cornea transparency. Both liposomes resulted in small, spherical shapes, with suitable physicochemical properties for the ocular administration. Lα-PC led to higher flux, permeation, and retention in the sclera, whereas POPE:POPG led to higher flux and permeation in the cornea. The formulations showed no irritant effects on the chorioallantoic membrane. Additionally, the liposomes did not affect the cornea transparency when they were applied, and the histological analysis did not reveal any structural alteration.
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Affiliation(s)
- Núria Garrós
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
| | - Mireia Mallandrich
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
- Institute of Nanoscience and nanotechnology, University of Barcelona, 645 Diagonal Avenue, 08028 Barcelona, Spain
- Correspondence:
| | - Negar Beirampour
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
| | - Roya Mohammadi
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
- Institute of Nanoscience and nanotechnology, University of Barcelona, 645 Diagonal Avenue, 08028 Barcelona, Spain
| | - Òscar Domènech
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
- Institute of Nanoscience and nanotechnology, University of Barcelona, 645 Diagonal Avenue, 08028 Barcelona, Spain
| | - Maria José Rodríguez-Lagunas
- Department of Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, Av. Joan XXIII, 08028 Barcelona, Spain
| | - Beatriz Clares
- Institute of Nanoscience and nanotechnology, University of Barcelona, 645 Diagonal Avenue, 08028 Barcelona, Spain
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
| | - Helena Colom
- Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
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15
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Functionalization of Nanoparticulate Drug Delivery Systems and Its Influence in Cancer Therapy. Pharmaceutics 2022; 14:pharmaceutics14051113. [PMID: 35631699 PMCID: PMC9145684 DOI: 10.3390/pharmaceutics14051113] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Revised: 05/11/2022] [Accepted: 05/19/2022] [Indexed: 12/13/2022] Open
Abstract
Research into the application of nanocarriers in the delivery of cancer-fighting drugs has been a promising research area for decades. On the other hand, their cytotoxic effects on cells, low uptake efficiency, and therapeutic resistance have limited their therapeutic use. However, the urgency of pressing healthcare needs has resulted in the functionalization of nanoparticles' (NPs) physicochemical properties to improve clinical outcomes of new, old, and repurposed drugs. This article reviews recent research on methods for targeting functionalized nanoparticles to the tumor microenvironment (TME). Additionally, the use of relevant engineering techniques for surface functionalization of nanocarriers (liposomes, dendrimers, and mesoporous silica) and their critical roles in overcoming the current limitations in cancer therapy-targeting ligands used for targeted delivery, stimuli strategies, and multifunctional nanoparticles-were all reviewed. The limitations and future perspectives of functionalized nanoparticles were also finally discussed. Using relevant keywords, published scientific literature from all credible sources was retrieved. A quick search of the literature yielded almost 400 publications. The subject matter of this review was addressed adequately using an inclusion/exclusion criterion. The content of this review provides a reasonable basis for further studies to fully exploit the potential of these nanoparticles in cancer therapy.
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Jurczyk M, Kasperczyk J, Wrześniok D, Beberok A, Jelonek K. Nanoparticles Loaded with Docetaxel and Resveratrol as an Advanced Tool for Cancer Therapy. Biomedicines 2022; 10:biomedicines10051187. [PMID: 35625921 PMCID: PMC9138983 DOI: 10.3390/biomedicines10051187] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/16/2022] [Accepted: 05/17/2022] [Indexed: 02/01/2023] Open
Abstract
A growing interest in the use of a combination of chemosensitizers and cytostatics for overcoming cancer resistance to treatment and the development of their delivery systems has been observed. Resveratrol (Res) presents antioxidant, anti-inflammatory and chemopreventive properties but also limits multidrug resistance against docetaxel (Dtx), which is one of the main causes of failure in cancer therapy with this drug. However, the use of both drugs presents challenges, including poor bioavailability, the unfavourable pharmacokinetics and chemical instability of Res and the poor water solubility and dose-limiting toxicity of Dtx. In order to overcome these difficulties, attempts have been made to create different forms of delivery for both agents. This review is focused on the latest developments in nanoparticles for the delivery of Dtx, Res and for the combined delivery of those two drugs. The aim of this review was also to summarize the synergistic mechanism of action of Dtx and Res on cancer cells. According to recent reports, Dtx and Res loaded in a nano-delivery system exhibit better efficiency in cancer treatment compared to free drugs. Also, the co-delivery of Dtx and Res in one actively targeted delivery system providing the simultaneous release of both drugs in cancer cells has a chance to fulfil the requirements of effective anticancer therapy and reduce limitations in therapy caused by multidrug resistance (MDR).
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Affiliation(s)
- Magdalena Jurczyk
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Skłodowska 34 St., 41-819 Zabrze, Poland; (M.J.); (J.K.)
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland; (D.W.); (A.B.)
| | - Janusz Kasperczyk
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Skłodowska 34 St., 41-819 Zabrze, Poland; (M.J.); (J.K.)
- Department of Biopharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jedności 8, 41-200 Sosnowiec, Poland
| | - Dorota Wrześniok
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland; (D.W.); (A.B.)
| | - Artur Beberok
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland; (D.W.); (A.B.)
| | - Katarzyna Jelonek
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Curie-Skłodowska 34 St., 41-819 Zabrze, Poland; (M.J.); (J.K.)
- Correspondence: ; Tel.: +48-32-271-2969
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Sarkar S, De S. Brij Niosomes as Carriers for Sustained Drug Delivery─A Fluorescence-Based Approach to Probe the Niosomal Microenvironment. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2022; 38:4521-4537. [PMID: 35377656 DOI: 10.1021/acs.langmuir.1c02996] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Niosomes were prepared using a triad of polyoxyethylene alkyl ether surfactants. The focus was to elucidate the effects of varying alkyl chain length and varying hydrophilic headgroups on the structure of the niosomes, with an aim to design niosomes for efficient encapsulation and release of both hydrophobic and hydrophilic drugs. The phase transitions of the surfactants were ascertained by differential scanning calorimetry. It was found that the headgroup has a profound influence on the niosomal bilayer. Fluorescent probes Coumarin 153 (C-153) and 1,6-diphenyl-1,3,5-hexatriene were used to probe the structural integrity of the niosomal bilayer under stress conditions. Other aspects of the niosomes were probed by following the aggregation of the dyes fluorescein (FL) and Nile Red, red edge excitation shift, and fluorescence resonance energy transfer (FRET) between them. Fluorescence lifetime imaging microscopy provides proof of the exact location of the donor and acceptor dyes in the niosomes under FRET condition. It was also shown that the niosomes are efficient "carriers" for entrapment and controlled release of the chemotherapeutic drug 5-fluorouracil. It was found that a rigid niosomal bilayer leads to controlled drug release. The present work is relevant for the future use of these niosomes for cargo entrapment.
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Affiliation(s)
- Sudeshna Sarkar
- Department of Chemistry, University of Kalyani, Kalyani, West Bengal 741235, India
| | - Swati De
- Department of Chemistry, University of Kalyani, Kalyani, West Bengal 741235, India
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García-Hevia L, Casafont Í, Oliveira J, Terán N, Fanarraga ML, Gallo J, Bañobre-López M. Magnetic lipid nanovehicles synergize the controlled thermal release of chemotherapeutics with magnetic ablation while enabling non-invasive monitoring by MRI for melanoma theranostics. Bioact Mater 2022; 8:153-164. [PMID: 34541393 PMCID: PMC8424388 DOI: 10.1016/j.bioactmat.2021.06.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 05/20/2021] [Accepted: 06/07/2021] [Indexed: 01/13/2023] Open
Abstract
Nowadays, a number of promising strategies are being developed that aim at combining diagnostic and therapeutic capabilities into clinically effective formulations. Thus, the combination of a modified release provided by an organic encapsulation and the intrinsic physico-chemical properties from an inorganic counterpart opens new perspectives in biomedical applications. Herein, a biocompatible magnetic lipid nanocomposite vehicle was developed through an efficient, green and simple method to simultaneously incorporate magnetic nanoparticles and an anticancer drug (doxorubicin) into a natural nano-matrix. The theranostic performance of the final magnetic formulation was validated in vitro and in vivo, in melanoma tumors. The systemic administration of the proposed magnetic hybrid nanocomposite carrier enhanced anti-tumoral activity through a synergistic combination of magnetic hyperthermia effects and antimitotic therapy, together with MRI reporting capability. The application of an alternating magnetic field was found to play a dual role, (i) acting as an extra layer of control (remote, on-demand) over the chemotherapy release and (ii) inducing a local thermal ablation of tumor cells. This combination of chemotherapy with thermotherapy establishes a synergistic platform for the treatment of solid malignant tumors under lower drug dosing schemes, which may realize the dual goal of reduced systemic toxicity and enhanced anti-tumoral efficacy.
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Affiliation(s)
- Lorena García-Hevia
- Advanced (Magnetic) Theranostic Nanostructures Lab. International Iberian Nanotechnology Laboratory, Avda. Mestre José Veiga s/n, 4715-330, Braga, Portugal
| | - Íñigo Casafont
- Grupo de Nanomedicina. Universidad de Cantabria-IDIVAL, Herrera Oria s/n, 39011, Santander, Spain
| | - Jessica Oliveira
- Advanced (Magnetic) Theranostic Nanostructures Lab. International Iberian Nanotechnology Laboratory, Avda. Mestre José Veiga s/n, 4715-330, Braga, Portugal
| | - Nuria Terán
- Grupo de Nanomedicina. Universidad de Cantabria-IDIVAL, Herrera Oria s/n, 39011, Santander, Spain
| | - Mónica L. Fanarraga
- Grupo de Nanomedicina. Universidad de Cantabria-IDIVAL, Herrera Oria s/n, 39011, Santander, Spain
| | - Juan Gallo
- Advanced (Magnetic) Theranostic Nanostructures Lab. International Iberian Nanotechnology Laboratory, Avda. Mestre José Veiga s/n, 4715-330, Braga, Portugal
| | - Manuel Bañobre-López
- Advanced (Magnetic) Theranostic Nanostructures Lab. International Iberian Nanotechnology Laboratory, Avda. Mestre José Veiga s/n, 4715-330, Braga, Portugal
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Sriwidodo, Umar AK, Wathoni N, Zothantluanga JH, Das S, Luckanagul JA. Liposome-polymer complex for drug delivery system and vaccine stabilization. Heliyon 2022; 8:e08934. [PMID: 35243059 PMCID: PMC8861389 DOI: 10.1016/j.heliyon.2022.e08934] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 01/25/2022] [Accepted: 02/08/2022] [Indexed: 12/18/2022] Open
Abstract
Liposomes have been used extensively as micro- and nanocarriers for hydrophobic or hydrophilic molecules. However, conventional liposomes are biodegradable and quickly eliminated, making it difficult to be used for delivery in specific routes, such as the oral and systemic routes. One way to overcome this problem is through complexation with polymers, which is referred to as a liposome complex. The use of polymers can increase the stability of liposome with regard to pH, chemicals, enzymes, and the immune system. In some cases, specific polymers can condition the properties of liposomes to be explicitly used in drug delivery, such as targeted delivery and controlled release. These properties are influenced by the type of polymer, crosslinker, interaction, and bond in the complexation process. Therefore, it is crucial to study and review these parameters for the development of more optimal forms and properties of the liposome complex. This article discusses the use of natural and synthetic polymers, ways of interaction between polymers and liposomes (on the surface, incorporation in lamellar chains, and within liposomes), types of bonds, evaluation standards, and their effects on the stability and pharmacokinetic profile of the liposome complex, drugs, and vaccines. This article concludes that both natural and synthetic polymers can be used in modifying the structure and physicochemical properties of liposomes to specify their use in targeted delivery, controlled release, and stabilizing drugs and vaccines.
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Affiliation(s)
- Sriwidodo
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
| | - Abd. Kakhar Umar
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
- Department of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Nasrul Wathoni
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia
| | - James H. Zothantluanga
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, Assam, India
| | - Sanjoy Das
- Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, Assam, India
| | - Jittima Amie Luckanagul
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
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Salari N, Rasoulpoor S, Valipour E, Mansouri K, Bartina Y, Dokaneheifard S, Mohammadi M, Abam F. Liposomes, new carriers for delivery of genes and anticancer drugs: a systematic review. Anticancer Drugs 2022; 33:e9-e20. [PMID: 34282743 DOI: 10.1097/cad.0000000000001144] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Today, nanoscience has grown and developed in various fields of medicine and treatment, including cancer treatment. Currently, the existing treatments, including chemotherapy and radiotherapy, cause side effects that are unpleasant to the patient. Due to the fact that anticancer drugs cause severe and widespread side effects, liposomes are considered as new drug carriers to minimize the untimely destruction of the drug when it is delivered to the target tissue and to prevent the side effects of toxic drugs. This systematic review study examined the importance of using liposomes as new drug carriers for the delivery of genes and anticancer drugs. The articles published in English in the databases of Google scholar, WoS, PubMed, Embase, Scopus and science direct were reviewed. According to the results of this study, a new targeted nanosystem has been used for loading and delivering anticancer drugs, genes and controlled drug release which has a significant therapeutic effect compared to the same amount of free drug. In general, liposomal systems have been considered because of their capability in preserving the effect of the drug along with reducing the side effects and toxicity of the drug, especially in the case of anticancer drugs. Accumulation of the drug in a target tissue which results in a reduction of the drug entry into other tissues is the main reason for reducing the side effects of these drugs.
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Affiliation(s)
| | - Shna Rasoulpoor
- Department of Medical Biology, Medical Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah
| | - Elahe Valipour
- Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Kamran Mansouri
- Department of Medical Biology, Medical Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah
| | - Yalda Bartina
- Department of Translation Studies, Faculty of Literature, Istanbul University, Istanbul, Turkey
| | - Sadat Dokaneheifard
- Department of Human Genetics, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Masoud Mohammadi
- Department of Nursing, School of Nursing and Midwifery, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farzaneh Abam
- Department of Medical Biology, Medical Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah
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Darroudi M, Gholami M, Rezayi M, Khazaei M. An overview and bibliometric analysis on the colorectal cancer therapy by magnetic functionalized nanoparticles for the responsive and targeted drug delivery. J Nanobiotechnology 2021; 19:399. [PMID: 34844632 PMCID: PMC8630862 DOI: 10.1186/s12951-021-01150-6] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/19/2021] [Indexed: 12/27/2022] Open
Abstract
With the growing demands for personalized medicine and medical devices, nanomedicine is a modern scientific field, and research continues to apply nanomaterials for therapeutic and damaged tissue diagnosis. In this regard, substantial progress has been made in synthesizing magnetic nanoparticles with desired sizes, chemical composition, morphologies, and surface chemistry. Among these materials, nanomagnetic iron oxides have demonstrated promise as unique drug delivery carriers due to cancer treatment. This carrier could lead to responsive properties to a specific trigger, including heat, pH, alternative magnetic field, or even enzymes, through functionalization and coating of magnetic nanoparticles, along with biocompatibility, good chemical stability, easy functionalization, simple processing, and ability to localize to the tumor site with the assistance of external magnetic field. Current studies have focused on magnetic nanoparticles' utilities in cancer therapy, especially for colorectal cancer. Additionally, a bibliometric investigation was performed on the public trends in the field of the magnetic nanoparticle to drug delivery and anticancer, which represented progressing applications of these carriers in the multidisciplinary zones with a general view on future research and identified potential opportunities and challenges. Furthermore, we outline the current challenges and forthcoming research perspective for high performance and fostering advanced MNPs in colorectal cancer treatment.
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Affiliation(s)
- Mahdieh Darroudi
- Department of Medical Biotechnology and Nanotechnology, School of Science, Mashhad University of Medical Science, Mashhad, Iran.,Department of Physiology, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Mehrdad Gholami
- Department of Chemistry, Marvdasht Branch, Islamic Azad University, P.O. Box 465, Marvdasht, Iran
| | - Majid Rezayi
- Department of Medical Biotechnology and Nanotechnology, School of Science, Mashhad University of Medical Science, Mashhad, Iran. .,Medical Toxicology Research Center, Mashhad University of Medical Science, Mashhad, Iran. .,Metabolic Syndrome Research Center, Mashhad University of Medical Science, Mashhad, Iran.
| | - Majid Khazaei
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran. .,Metabolic Syndrome Research Center, Mashhad University of Medical Science, Mashhad, Iran.
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22
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Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid Nanoparticles─From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement. ACS NANO 2021; 15:16982-17015. [PMID: 34181394 DOI: 10.1021/acsnano.1c04996] [Citation(s) in RCA: 1039] [Impact Index Per Article: 259.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
Lipid nanoparticles (LNPs) have emerged across the pharmaceutical industry as promising vehicles to deliver a variety of therapeutics. Currently in the spotlight as vital components of the COVID-19 mRNA vaccines, LNPs play a key role in effectively protecting and transporting mRNA to cells. Liposomes, an early version of LNPs, are a versatile nanomedicine delivery platform. A number of liposomal drugs have been approved and applied to medical practice. Subsequent generations of lipid nanocarriers, such as solid lipid nanoparticles, nanostructured lipid carriers, and cationic lipid-nucleic acid complexes, exhibit more complex architectures and enhanced physical stabilities. With their ability to encapsulate and deliver therapeutics to specific locations within the body and to release their contents at a desired time, LNPs provide a valuable platform for treatment of a variety of diseases. Here, we present a landscape of LNP-related scientific publications, including patents and journal articles, based on analysis of the CAS Content Collection, the largest human-curated collection of published scientific knowledge. Rising trends are identified, such as nanostructured lipid carriers and solid lipid nanoparticles becoming the preferred platforms for numerous formulations. Recent advancements in LNP formulations as drug delivery platforms, such as antitumor and nucleic acid therapeutics and vaccine delivery systems, are discussed. Challenges and growth opportunities are also evaluated in other areas, such as medical imaging, cosmetics, nutrition, and agrochemicals. This report is intended to serve as a useful resource for those interested in LNP nanotechnologies, their applications, and the global research effort for their development.
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Affiliation(s)
- Rumiana Tenchov
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Robert Bird
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Allison E Curtze
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Qiongqiong Zhou
- CAS, a division of the American Chemical Society, Columbus, Ohio 43210, United States
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23
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Application of Non-Viral Vectors in Drug Delivery and Gene Therapy. Polymers (Basel) 2021; 13:polym13193307. [PMID: 34641123 PMCID: PMC8512075 DOI: 10.3390/polym13193307] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Revised: 09/15/2021] [Accepted: 09/18/2021] [Indexed: 12/13/2022] Open
Abstract
Vectors and carriers play an indispensable role in gene therapy and drug delivery. Non-viral vectors are widely developed and applied in clinical practice due to their low immunogenicity, good biocompatibility, easy synthesis and modification, and low cost of production. This review summarized a variety of non-viral vectors and carriers including polymers, liposomes, gold nanoparticles, mesoporous silica nanoparticles and carbon nanotubes from the aspects of physicochemical characteristics, synthesis methods, functional modifications, and research applications. Notably, non-viral vectors can enhance the absorption of cargos, prolong the circulation time, improve therapeutic effects, and provide targeted delivery. Additional studies focused on recent innovation of novel synthesis techniques for vector materials. We also elaborated on the problems and future research directions in the development of non-viral vectors, which provided a theoretical basis for their broad applications.
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Bhusnure OG, Gholve SB, Giram PS, Gaikwad AV, Udumansha U, Mani G, Tae JH. Novel 5-flurouracil-Embedded non-woven PVA - PVP electrospun nanofibers with enhanced anti-cancer efficacy: Formulation, evaluation and in vitro anti-cancer activity. J Drug Deliv Sci Technol 2021. [DOI: 10.1016/j.jddst.2021.102654] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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25
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Fernández-Álvarez F, Caro C, García-García G, García-Martín ML, Arias JL. Engineering of stealth (maghemite/PLGA)/chitosan (core/shell)/shell nanocomposites with potential applications for combined MRI and hyperthermia against cancer. J Mater Chem B 2021; 9:4963-4980. [PMID: 34114575 DOI: 10.1039/d1tb00354b] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
(Maghemite/poly(d,l-lactide-co-glycolide))/chitosan (core/shell)/shell nanoparticles have been prepared reproducibly by nanoprecipitation solvent evaporation plus coacervation (production performance ≈ 45%, average size ≈ 325 nm). Transmission electron microscopy, energy dispersive X-ray spectroscopy, electrophoretic determinations, and X-ray diffraction patterns demonstrated the satisfactory embedment of iron oxide nanocores within the solid polymer matrix and the formation of an external shell of chitosan in the nanostructure. The adequate magnetic responsiveness of the nanocomposites was characterized in vitro by hysteresis cycle determinations and by visualization of the nanosystem under the influence of a 0.4 T permanent magnet. Safety and biocompatibility of the (core/shell)/shell particles were based on in vitro haemocompatibility studies and cytotoxicity tests against HFF-1 human foreskin fibroblasts and on ex vivo toxicity assessments on tissue samples from Balb/c mice. Transversal relaxivities, determined in vitro at a low magnetic field of 1.44 T, demonstrated their capability as T2 contrast agents for magnetic resonance imaging, being comparable to that of some iron oxide-based contrast agents. Heating properties were evaluated in a high frequency alternating electromagnetic gradient: a constant maximum temperature of ≈46 °C was generated within ≈50 min, while antitumour hyperthermia tests on T-84 colonic adenocarcinoma cells proved the relevant decrease in cell viability (to ≈ 39%) when treated with the nanosystem under the influence of that electromagnetic field. Finally, in vivo magnetic resonance imaging studies and ex vivo histology determinations of iron deposits postulated the efficacy of chitosan to provide long-circulating capabilities to the nanocomposites, retarding nanoparticle recognition by the mononuclear phagocyte system. To our knowledge, this is the first study describing such a type of biocompatible and long-circulating nanoplatform with promising theranostic applications (biomedical imaging and hyperthermia) against cancer.
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Affiliation(s)
- Fátima Fernández-Álvarez
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain.
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26
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Jurczyk M, Jelonek K, Musiał-Kulik M, Beberok A, Wrześniok D, Kasperczyk J. Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery. Pharmaceutics 2021; 13:326. [PMID: 33802531 PMCID: PMC8001342 DOI: 10.3390/pharmaceutics13030326] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 02/10/2021] [Accepted: 02/25/2021] [Indexed: 12/19/2022] Open
Abstract
Cancer is one of the major causes of death worldwide and its treatment remains very challenging. The effectiveness of cancer therapy significantly depends upon tumour-specific delivery of the drug. Nanoparticle drug delivery systems have been developed to avoid the side effects of the conventional chemotherapy. However, according to the most recent recommendations, future nanomedicine should be focused mainly on active targeting of nanocarriers based on ligand-receptor recognition, which may show better efficacy than passive targeting in human cancer therapy. Nevertheless, the efficacy of single-ligand nanomedicines is still limited due to the complexity of the tumour microenvironment. Thus, the NPs are improved toward an additional functionality, e.g., pH-sensitivity (advanced single-targeted NPs). Moreover, dual-targeted nanoparticles which contain two different types of targeting agents on the same drug delivery system are developed. The advanced single-targeted NPs and dual-targeted nanocarriers present superior properties related to cell selectivity, cellular uptake and cytotoxicity toward cancer cells than conventional drug, non-targeted systems and single-targeted systems without additional functionality. Folic acid and biotin are used as targeting ligands for cancer chemotherapy, since they are available, inexpensive, nontoxic, nonimmunogenic and easy to modify. These ligands are used in both, single- and dual-targeted systems although the latter are still a novel approach. This review presents the recent achievements in the development of single- or dual-targeted nanoparticles for anticancer drug delivery.
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Affiliation(s)
- Magdalena Jurczyk
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 41-819 Zabrze, Poland; (M.J.); (M.M.-K.); (J.K.)
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland; (A.B.); (D.W.)
| | - Katarzyna Jelonek
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 41-819 Zabrze, Poland; (M.J.); (M.M.-K.); (J.K.)
| | - Monika Musiał-Kulik
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 41-819 Zabrze, Poland; (M.J.); (M.M.-K.); (J.K.)
| | - Artur Beberok
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland; (A.B.); (D.W.)
| | - Dorota Wrześniok
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland; (A.B.); (D.W.)
| | - Janusz Kasperczyk
- Centre of Polymer and Carbon Materials, Polish Academy of Sciences, 41-819 Zabrze, Poland; (M.J.); (M.M.-K.); (J.K.)
- Department of Biopharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 41-200 Sosnowiec, Poland
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Gemcitabine-Loaded Magnetically Responsive Poly( ε-caprolactone) Nanoparticles against Breast Cancer. Polymers (Basel) 2020; 12:polym12122790. [PMID: 33255803 PMCID: PMC7761181 DOI: 10.3390/polym12122790] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 11/19/2020] [Accepted: 11/23/2020] [Indexed: 12/14/2022] Open
Abstract
A reproducible and efficient interfacial polymer disposition method has been used to formulate magnetite/poly(ε-caprolactone) (core/shell) nanoparticles (average size ≈ 125 nm, production performance ≈ 90%). To demonstrate that the iron oxide nuclei were satisfactorily embedded within the polymeric solid matrix, a complete analysis of these nanocomposites by, e.g., electron microscopy visualizations, energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, electrophoresis, and contact angle goniometry was conducted. The magnetic responsive behaviour of these nanoparticles was quantitatively characterized by the hysteresis cycle and qualitatively investigated by visualization of the colloid under exposure to a 0.4 T magnet. Gemcitabine entrapment into the polymeric shell reported adequate drug loading values (≈11%), and a biphasic and pH-responsive drug release profile (≈ four-fold faster Gemcitabine release at pH 5.0 compared to pH 7.4). Cytotoxicity studies in MCF-7 human breast cancer cells proved that the half maximal inhibitory concentration of Gem-loaded nanocomposites was ≈ two-fold less than that of the free drug. Therefore, these core/shell nanoparticles could have great possibilities as a magnetically targeted Gemcitabine delivery system for breast cancer treatment.
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Sola-Leyva A, Jabalera Y, Chico-Lozano MA, Carrasco-Jiménez MP, Iglesias GR, Jimenez-Lopez C. Reactive oxygen species (ROS) production in HepG2 cancer cell line through the application of localized alternating magnetic field. J Mater Chem B 2020; 8:7667-7676. [PMID: 32705099 DOI: 10.1039/d0tb01306d] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Recent studies have shown the potential of magnetic hyperthermia in cancer treatments. However, the underlying mechanisms involved have not been yet fully described. In particular, the cell death related to magnetic hyperthermia observed in cultures incubated with low concentration of magnetic nanoparticles and under a low intensity alternating magnetic field, in which a macroscopic temperature rise is not observed, is still not understood. In the present study, we investigate the production of intracellular Reactive Oxygen Species (ROS) as a mechanism to induce cell death under these conditions. In this study, the production and influence of ROS on the viability of HepG2 human hepatoma cells (used as a model cell line) are analyzed under the application of variable magnetic fields using hyperthermia agents, such as biomimetic magnetic nanoparticles (BMNPs) mediated by magnetosome MamC protein from Magnetococcus marinus MC-1. The results show that intracellular ROS production increases up to ∼90% following upon the exposure of AMF to HepG2 cells containing BMNPs, which could determine the loss of cell viability (up to ∼40% reduction) without a significant rise in temperature. Such ROS production is linked to mitochondrial dysfunction caused by the application of AMF to cells containing BMNPs.
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Affiliation(s)
- Alberto Sola-Leyva
- Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain.
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29
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Biomimetic Magnetoliposomes as Oxaliplatin Nanocarriers: In Vitro Study for Potential Application in Colon Cancer. Pharmaceutics 2020; 12:pharmaceutics12060589. [PMID: 32599905 PMCID: PMC7356838 DOI: 10.3390/pharmaceutics12060589] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 06/22/2020] [Accepted: 06/23/2020] [Indexed: 12/24/2022] Open
Abstract
Current chemotherapy for colorectal cancer (CRC) includes the use of oxaliplatin (Oxa), a first-line cytotoxic drug which, in combination with irinotecan/5-fluorouracil or biologic agents, increases the survival rate of patients. However, the administration of this drug induces side effects that limit its application in patients, making it necessary to develop new tools for targeted chemotherapy. MamC-mediated biomimetic magnetic nanoparticles coupled with Oxa (Oxa-BMNPs) have been previously demonstrated to efficiently reduce the IC50 compared to that of soluble Oxa. However, their strong interaction with the macrophages revealed toxicity and possibility of aggregation. In this scenario, a further improvement of this nanoassembly was necessary. In the present study, Oxa-BMNPs nanoassemblies were enveloped in phosphatidylcholine unilamellar liposomes (both pegylated and non-pegylated). Our results demonstrate that the addition of both a lipid cover and further pegylation improves the biocompatibility and cellular uptake of the Oxa-BMNPs nanoassemblies without significantly reducing their cytotoxic activity in colon cancer cells. In particular, with the pegylated magnetoliposome nanoformulation (a) hemolysis was reduced from 5% to 2%, being now hematocompatibles, (b) red blood cell agglutination was reduced, (c) toxicity in white blood cells was eliminated. This study represents a truly stepforward in this area as describes the production of one of the very few existing nanoformulations that could be used for a local chemotherapy to treat CRC.
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30
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Ahmadifard Z, Ahmeda A, Rasekhian M, Moradi S, Arkan E. Chitosan-coated magnetic solid lipid nanoparticles for controlled release of letrozole. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101621] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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31
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Farid RM, Gaafar PM, Hazzah HA, Helmy MW, Abdallah OY. Chemotherapeutic potential of L-carnosine from stimuli-responsive magnetic nanoparticles against breast cancer model. Nanomedicine (Lond) 2020; 15:891-911. [DOI: 10.2217/nnm-2019-0428] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Aim: L-carnosine-coated magnetic nanoparticles (CCMNPs) were developed to enhance chemotherapeutic activity of carnosine-dipeptide. Materials & methods: Surface grafting of MNPs with carnosine was contended by differential scanning calorimetry, infrared spectroscopy and x-ray diffraction. Physicochemical characterization and in vitro cytotoxicity on MCF-7 cell line was carried out. In vivo chemotherapeutic activity and toxicity was assessed by an Ehrlich Ascites tumor model. Results: CCMNPs possessed monodispersed size (120 nm), ζ (-27.3 mV), magnetization (51.52 emu/g) and entrapment efficiency (88.3%) with sustained release rate. CCMNPs showed 2.3-folds lower IC50 values compared with carnosine solution after 48 h. Targeted CCMNPs were specifically accumulated in tumor showing significant reduction in tumor size with no systemic toxicity. Significant reduction in VEGF and cyclin D1 levels were observed. Conclusion: The developed system endowed with responsiveness to an external stimulus can represent a promising magnetically targeted delivery system for carnosine site specific delivery.
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Affiliation(s)
- Ragwa M Farid
- Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt
| | - Passent M E Gaafar
- Department of Pharmaceutics, College of Pharmacy, Arab Academy for Science, Technology & Maritime Transport, Alexandria, Egypt
| | - Heba A Hazzah
- Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt
| | - Maged W Helmy
- Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| | - Ossama Y Abdallah
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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Das M, Huang L. Liposomal Nanostructures for Drug Delivery in Gastrointestinal Cancers. J Pharmacol Exp Ther 2019; 370:647-656. [PMID: 30541917 PMCID: PMC6812858 DOI: 10.1124/jpet.118.254797] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Accepted: 12/11/2018] [Indexed: 12/19/2022] Open
Abstract
Gastrointestinal (GI) cancers like liver, pancreatic, colorectal, and gastric cancer remain some of the most difficult and aggressive cancers. Nanoparticles like liposomes had been approved in the clinic for cancer therapy dating as far back as 1995. Over the years, liposomal formulations have come a long way, facing several roadblocks and failures, and advancing by optimizing formulations and incorporating novel design approaches to navigate therapeutic delivery challenges. The first liposomal formulation for a GI cancer drug was approved recently in 2015, setting the stage for further clinical developments of liposome-based delivery systems for therapies against GI malignancies. This article reviews the design considerations and strategies that can be used to deliver drugs to GI tumors, the wide range of therapeutic agents that have been explored in preclinical as well as clinical studies, and the current therapies that are being investigated in the clinic against GI malignancies.
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Affiliation(s)
- Manisit Das
- Division of Pharmacoengineering and Molecular Pharmaceutics, and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Leaf Huang
- Division of Pharmacoengineering and Molecular Pharmaceutics, and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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Ebadi M, Saifullah B, Buskaran K, Hussein MZ, Fakurazi S. Synthesis and properties of magnetic nanotheranostics coated with polyethylene glycol/5-fluorouracil/layered double hydroxide. Int J Nanomedicine 2019; 14:6661-6678. [PMID: 31695362 PMCID: PMC6707435 DOI: 10.2147/ijn.s214923] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Accepted: 07/25/2019] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Cancer treatments are being continually developed. Increasingly more effective and better-targeted treatments are available. As treatment has developed, the outcomes have improved. PURPOSE In this work, polyethylene glycol (PEG), layered double hydroxide (LDH) and 5-fluorouracil (5-FU) were used as a stabilizing agent, a carrier and an anticancer active agent, respectively. CHARACTERIZATION AND METHODS Magnetite nanoparticles (Fe3O4) coated with polyethylene glycol (PEG) and co-coated with 5-fluorouracil/Mg/Al- or Zn/Al-layered double hydroxide were synthesized by co-precipitation technique. Structural, magnetic properties, particle shape, particle size and drug loading percentage of the magnetic nanoparticles were investigated by XRD, TGA, FTIR, DLS, FESEM, TEM, VSM, UV-vis spectroscopy and HPLC techniques. RESULTS XRD, TGA and FTIR studies confirmed the formation of Fe3O4 phase and the presence of iron oxide nanoparticles, polyethylene glycol, LDH and the drug for all the synthesized samples. The size of the nanoparticles co-coated with Mg/Al-LDH is about 27 nm compared to 40 nm when they were co-coated with Zn/Al-LDH, with both showings near uniform spherical shape. The iron oxide nanoparticles retain their superparamagnetic property when they were coated with polyethylene glycol, polyethylene glycol co-coated with Mg/Al-LDH and polyethylene glycol co-coated with Zn/Al-LDH with magnetic saturation value of 56, 40 and 27 emu/g, respectively. The cytotoxicity study reveals that the anticancer nanodelivery system has better anticancer activity than the free drug, 5-FU against liver cancer HepG2 cells and at the same time, it was found to be less toxic to the normal fibroblast 3T3 cells. CONCLUSION These are unique core-shell nanoparticles synthesized with the presence of multiple functionalities are hoped can be used as a multifunctional nanocarrier with the capability of targeted delivery using an external magnetic field and can also be exploited as hypothermia for cancer cells in addition to the chemotherapy property.
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Affiliation(s)
- Mona Ebadi
- Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Bullo Saifullah
- Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
- Laboratory for Vaccine and Immunotherapeutic, Institute of Biosciences, Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Kalaivani Buskaran
- Laboratory for Vaccine and Immunotherapeutic, Institute of Biosciences, Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Mohd Zobir Hussein
- Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
| | - Sharida Fakurazi
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor43400, Malaysia
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Jabalera Y, Fernández-Vivas A, Iglesias GR, Delgado ÁV, Jimenez-Lopez C. Magnetoliposomes of mixed biomimetic and inorganic magnetic nanoparticles as enhanced hyperthermia agents. Colloids Surf B Biointerfaces 2019; 183:110435. [PMID: 31430636 DOI: 10.1016/j.colsurfb.2019.110435] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/29/2019] [Accepted: 08/07/2019] [Indexed: 10/26/2022]
Abstract
Recently, liposomes have been explored as a potential solution to improve the biocompatibility and the colloidal stability of magnetic nanoparticles. Protocols have been developed for producing magnetoliposomes of magnetite nanoparticles obtained inorganically (MNPs). However, the biomimetic synthesis of magnetite using heterologous proteins from magnetotactic bacteria has become a real alternative to produce novel biomimetic magnetic nanoparticles (BMNPs). Among these, the BMNPs obtained in presence of MamC protein from Magnetococcus marinus MC-1 have been proposed as excellent candidates to be potentially used as drug nanocarriers and as hyperthermia agents. However, their colloidal stability still needs to be improved while maintaining their magnetic properties intact. One possibility explored in this manuscript is to form magnetoliposomes that contain BMNPs. Indeed, the protocols developed for producing magnetoliposomes of MNPs need to be tested and modified to be able to include BMNPs. In this context, a protocol has been developed to produce both magnetoliposomes filled with MNPs and/or BMNPs and their potential as hyperthermia agents was tested. In fact, for the first time, these two types of nanoparticles were mixed in different proportions to test the composition that would optimize such as behaviour as hyperthermia agents. Interestingly, it was observed that the hyperthermia behaviour of the magnetoliposomes greatly improved if they were filled with a mixture of MNPs and BMNPs. These results indicate that these magnetoliposomes display optimal characteristics to become a potential agent for hyperthermia and that the opening of those liposomes could be externally controlled by applying an alternate magnetic field.
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Affiliation(s)
- Ylenia Jabalera
- Department of Microbiology, Faculty of Sciences, University of Granada, Spain
| | | | - Guillermo R Iglesias
- Department of Applied Physics, Faculty of Sciences, University of Granada, Spain
| | - Ángel V Delgado
- Department of Applied Physics, Faculty of Sciences, University of Granada, Spain
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35
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Silica Nanoparticles: Preparation, Characterization and Applications in Biomedicine. Pharm Chem J 2019. [DOI: 10.1007/s11094-019-02001-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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van Ballegooie C, Man A, Win M, Yapp DT. Spatially Specific Liposomal Cancer Therapy Triggered by Clinical External Sources of Energy. Pharmaceutics 2019; 11:E125. [PMID: 30884786 PMCID: PMC6470770 DOI: 10.3390/pharmaceutics11030125] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 03/12/2019] [Accepted: 03/13/2019] [Indexed: 11/25/2022] Open
Abstract
This review explores the use of energy sources, including ultrasound, magnetic fields, and external beam radiation, to trigger the delivery of drugs from liposomes in a tumor in a spatially-specific manner. Each section explores the mechanism(s) of drug release that can be achieved using liposomes in conjunction with the external trigger. Subsequently, the treatment's formulation factors are discussed, highlighting the parameters of both the therapy and the medical device. Additionally, the pre-clinical and clinical trials of each triggered release method are explored. Lastly, the advantages and disadvantages, as well as the feasibility and future outlook of each triggered release method, are discussed.
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Affiliation(s)
- Courtney van Ballegooie
- Experimental Therapeutics, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
- Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
| | - Alice Man
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
| | - Mi Win
- Department of Chemistry, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.
| | - Donald T Yapp
- Experimental Therapeutics, BC Cancer, Vancouver, BC V5Z 1L3, Canada.
- Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
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Dutta S, Moses JA, Anandharamakrishnan C. Encapsulation of Nutraceutical Ingredients in Liposomes and Their Potential for Cancer Treatment. Nutr Cancer 2019; 70:1184-1198. [DOI: 10.1080/01635581.2018.1557212] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Sayantani Dutta
- Computational Modeling and Nano Scale Processing Unit, Indian Institute of Food Processing Technology (IIFPT), Ministry of Food Processing Industries, Government of India, Thanjavur, Tamil Nadu, India
| | - Jeyan Arthur Moses
- Computational Modeling and Nano Scale Processing Unit, Indian Institute of Food Processing Technology (IIFPT), Ministry of Food Processing Industries, Government of India, Thanjavur, Tamil Nadu, India
| | - C. Anandharamakrishnan
- Computational Modeling and Nano Scale Processing Unit, Indian Institute of Food Processing Technology (IIFPT), Ministry of Food Processing Industries, Government of India, Thanjavur, Tamil Nadu, India
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38
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Fernandes C, Suares D, Yergeri MC. Tumor Microenvironment Targeted Nanotherapy. Front Pharmacol 2018; 9:1230. [PMID: 30429787 PMCID: PMC6220447 DOI: 10.3389/fphar.2018.01230] [Citation(s) in RCA: 91] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 10/08/2018] [Indexed: 12/12/2022] Open
Abstract
Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.
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Affiliation(s)
| | | | - Mayur C Yergeri
- Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies - NMIMS, Mumbai, India
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Formulation and in vitro evaluation of magnetoliposomes as a potential nanotool in colorectal cancer therapy. Colloids Surf B Biointerfaces 2018; 171:553-565. [PMID: 30096477 DOI: 10.1016/j.colsurfb.2018.07.070] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 06/27/2018] [Accepted: 07/30/2018] [Indexed: 12/11/2022]
Abstract
Magnetoliposomes (MLPs) offer many new possibilities in cancer therapy and diagnosis, including the transport of antitumor drugs, hyperthermia treatment, detection using imaging techniques, and even cell migration. However, high biocompatibility and functionality after cell internalization are essential to their successful application. We synthesized maghemite nanoparticles (γ-Fe2O3) by oxidizing magnetite cores (Fe3O4) and coating them with phosphatidylcholine (PC) liposomes, obtained using the thin film hydration method, to generate MLPs. The MLPs were tested in vitro, using human tumor and non-tumor colon cell lines, for cytotoxicity, cell uptake and cellular distribution, and magnetically-induced cell mobility. In addition, blood cells biocompatibility studies were performed. The mean size of the MLPs, with a core of γ-Fe2O3 completely surrounded by PC liposomes, was 90 ± 20 nm, showing a soft magnetic character and a great biocompatibility in all the cell lines assayed including blood cells. Prussian blue staining showed a high MLP cell uptake with maximum internalization at 24 h. TEM analysis showed the MLPs surrounded by the cell membrane and in the cell periphery, suggesting internalization by endocytosis and/or macropinocytosis. Interestingly, the mitochondria presented MLP accumulations, particularly in tumor cells. Finally, MLPs within colon cancer cells were able to induce cell migration when a magnetic field was applied in vitro, indicating the functionality of our nanoformulation. A promising biomedical application of these MLPs is anticipated based on their physical, chemical and biological properties.
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40
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Skouras A, Papadia K, Mourtas S, Klepetsanis P, Antimisiaris SG. Multifunctional doxorubicin-loaded magnetoliposomes with active and magnetic targeting properties. Eur J Pharm Sci 2018; 123:162-172. [PMID: 30041027 DOI: 10.1016/j.ejps.2018.07.044] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 07/12/2018] [Accepted: 07/20/2018] [Indexed: 01/30/2023]
Abstract
Multifunctional magnetoliposomes (MLs) with active and magnetic targeting potential are evaluated as platform systems for drug targeting applications. USPIO-encapsulating MLs are prepared by freeze drying/extrusion, decorated with one or two ligands for brain or cancer targeting (t-MLs), and actively loaded with Doxorubicin (DOX). MLs have mean diameters between 117 and 171 nm. Ligand attachment yields and DOX-loading efficiency are sufficiently high, 78-95% and 89-92%, respectively, while DOX loading and retention is not affected by co-entrapment of USPIOs, and USPIO loading/retention is not modulated by DOX. Attachment of ligands, also does not affect DOX or USPIO loading. Interestingly, MLs have high magnetophoretic mobility (MM) compared to free USPIOs, which is not affected by surface coating with PEG (up to 8 mol%), but is slightly reduced by Chol incorporation in their membrane, or when functional groups are immobilized on their surface. ML size, (directly related to number of USPIOs entrapped per vesicle), is the most important MM-determining factor. MM increases by 570% when ML size increases from 69 to 348 nm. Targeting potential of t-MLs is verified by enhanced: (i) transport across a cellular model of the blood-brain-barrier, and (ii) anti-proliferative effect towards B16 melanoma cells. The potential of further enhancing t-ML targeting magnetically is verified by additional enhancements of (i) and (ii), when experiments are performed under a permanent magnetic field.
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Affiliation(s)
- Athanasios Skouras
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece
| | - Konstantina Papadia
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece
| | - Spyridon Mourtas
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece
| | - Pavlos Klepetsanis
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece; Institute of Chemical Engineering Sciences, FORTH/ICE-HT, Rio 26506, Patras, Greece
| | - Sophia G Antimisiaris
- Laboratory of Pharmaceutical Technology, Dept. of Pharmacy, School of Health Sciences, University of Patras, Rio 26510, Greece; Institute of Chemical Engineering Sciences, FORTH/ICE-HT, Rio 26506, Patras, Greece.
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41
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Millart E, Lesieur S, Faivre V. Superparamagnetic lipid-based hybrid nanosystems for drug delivery. Expert Opin Drug Deliv 2018. [DOI: 10.1080/17425247.2018.1453804] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- E. Millart
- Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France
| | - S. Lesieur
- Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France
| | - V. Faivre
- Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France
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42
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Zheng XC, Ren W, Zhang S, Zhong T, Duan XC, Yin YF, Xu MQ, Hao YL, Li ZT, Li H, Liu M, Li ZY, Zhang X. The theranostic efficiency of tumor-specific, pH-responsive, peptide-modified, liposome-containing paclitaxel and superparamagnetic iron oxide nanoparticles. Int J Nanomedicine 2018; 13:1495-1504. [PMID: 29559778 PMCID: PMC5856286 DOI: 10.2147/ijn.s157082] [Citation(s) in RCA: 63] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Background In the present study, the tumor-specific, pH-responsive peptide H7K(R2)2-modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide nanoparticles (SPIO NPs), PTX/SPIO-SSL-H7K(R2)2, was prepared by using H7K(R2)2 as the targeting ligand, SPIO NPs as the magnetic resonance imaging (MRI) agent, PTX as antitumor drug. Methods The PTX/SPIO-SSL-H7K(R2)2 was prepared by a thin film hydration method. The characteristics of PTX/SPIO-SSL-H7K(R2)2 were evaluated. The targeting effect, MRI, and antitumor activity of PTX/SPIO-SSL-H7K(R2)2 were investigated detail in vitro and in vivo in human breast carcinoma MDA-MB-231 cell models. Results Our results of in vitro flow cytometry, in vivo imaging, and in vivo MR imaging confirmed the pH-responsive characteristic of H7K(R2)2 in MDA-MB-231 cell line in vitro and in vivo. The results of in vivo MRI and in vivo antitumor activity confirmed the theranostic effect of PTX/SPIO-SSL-H7K(R2)2 in MDA-MB-231 tumor-bearing model. Conclusion Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI.
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Affiliation(s)
- Xiu-Chai Zheng
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Wei Ren
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Shuang Zhang
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Ting Zhong
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Xiao-Chuan Duan
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Yi-Fan Yin
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Mei-Qi Xu
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Yan-Li Hao
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Zhan-Tao Li
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Hui Li
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Man Liu
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Zhuo-Yue Li
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
| | - Xuan Zhang
- Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.,Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China
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43
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Cardoso VF, Francesko A, Ribeiro C, Bañobre-López M, Martins P, Lanceros-Mendez S. Advances in Magnetic Nanoparticles for Biomedical Applications. Adv Healthc Mater 2018; 7. [PMID: 29280314 DOI: 10.1002/adhm.201700845] [Citation(s) in RCA: 330] [Impact Index Per Article: 47.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 09/28/2017] [Indexed: 12/17/2022]
Abstract
Magnetic nanoparticles (NPs) are emerging as an important class of biomedical functional nanomaterials in areas such as hyperthermia, drug release, tissue engineering, theranostic, and lab-on-a-chip, due to their exclusive chemical and physical properties. Although some works can be found reviewing the main application of magnetic NPs in the area of biomedical engineering, recent and intense progress on magnetic nanoparticle research, from synthesis to surface functionalization strategies, demands for a work that includes, summarizes, and debates current directions and ongoing advancements in this research field. Thus, the present work addresses the structure, synthesis, properties, and the incorporation of magnetic NPs in nanocomposites, highlighting the most relevant effects of the synthesis on the magnetic and structural properties of the magnetic NPs and how these effects limit their utilization in the biomedical area. Furthermore, this review next focuses on the application of magnetic NPs on the biomedical field. Finally, a discussion of the main challenges and an outlook of the future developments in the use of magnetic NPs for advanced biomedical applications are critically provided.
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Affiliation(s)
- Vanessa Fernandes Cardoso
- Centro de Física; Universidade do Minho; 4710-057 Braga Portugal
- MEMS-Microelectromechanical Systems Research Unit; Universidade do Minho; 4800-058 Guimarães Portugal
| | | | - Clarisse Ribeiro
- Centro de Física; Universidade do Minho; 4710-057 Braga Portugal
- CEB-Centre of Biological Engineering; University of Minho; Campus de Gualtar 4710-057 Braga Portugal
| | | | - Pedro Martins
- Centro de Física; Universidade do Minho; 4710-057 Braga Portugal
| | - Senentxu Lanceros-Mendez
- BCMaterials; Parque Científico y Tecnológico de Bizkaia; 48160 Derio Spain
- IKERBASQUE; Basque Foundation for Science; 48013 Bilbao Spain
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44
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Lorente C, Arias JL, Cabeza L, Ortiz R, Prados JC, Melguizo C, Delgado ÁV, Clares-Naveros B. Nano-engineering of biomedical prednisolone liposomes: evaluation of the cytotoxic effect on human colon carcinoma cell lines. J Pharm Pharmacol 2018; 70:488-497. [DOI: 10.1111/jphp.12882] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Accepted: 12/16/2017] [Indexed: 12/28/2022]
Abstract
Abstract
Objectives
Liposomes have attracted the attention of researchers due to their potential to act as drug delivery systems for cancer treatment. The present investigation aimed to develop liposomes loaded with prednisolone base and the evaluation of the antiproliferative effect on human colon carcinoma cell lines.
Methods
Liposomes were elaborated by following a reproducible thin film hydration technique. The physicochemical characterization of liposomes included photon correlation spectroscopy, microscopy analysis, Fourier transform infrared spectroscopy, rheological behaviour and electrophoresis. On the basis of these data and drug loading values, the best formulation was selected. Stability and drug release properties were also tested.
Key findings
Resulting liposomes exhibited optimal physicochemical and stability properties, an excellent haemocompatibility and direct antiproliferative effect on human colon carcinoma T-84 cell lines.
Conclusions
This study shows direct antitumour effect of prednisolone liposomal formulation, which opens the door for liposomal glucocorticoids as novel antitumour agents.
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Affiliation(s)
- Cristina Lorente
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
| | - José L Arias
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS)—University of Granada, Granada, Spain
| | - Laura Cabeza
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS)—University of Granada, Granada, Spain
| | - Raúl Ortiz
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain
| | - José C Prados
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS)—University of Granada, Granada, Spain
| | - Consolación Melguizo
- Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS)—University of Granada, Granada, Spain
| | - Ángel V Delgado
- Department of Applied Physics, Faculty of Sciences, University of Granada, Granada, Spain
| | - Beatriz Clares-Naveros
- Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Granada, Spain
- Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS)—University of Granada, Granada, Spain
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45
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Kono Y, Nakai T, Taguchi H, Fujita T. Development of magnetic anionic liposome/atelocollagen complexes for efficient magnetic drug targeting. Drug Deliv 2018; 24:1740-1749. [PMID: 29141461 PMCID: PMC8241088 DOI: 10.1080/10717544.2017.1402219] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Magnetic nanoparticle-incorporated liposomes (magnetic liposomes) are considered a promising site-specific drug delivery carrier vehicle. With regard to their surface charge, magnetic anionic liposomes (Mag-AL) demonstrate little toxicity in comparison with magnetic cationic liposomes (Mag-CL), whereas their cellular association and uptake efficiency are low. In the current study, we constructed complexes of Mag-AL and atelocollagen (ATCOL), which is a biocompatible and minimally immunogenic biomaterial, to improve the cellular uptake properties of Mag-AL in vitro and in vivo. The cellular association and/or uptake of Mag-AL in RAW264 cells, a murine macrophage-like cell line, under a magnetic field was significantly increased when Mag-AL was complexed with ATCOL, and the highest cellular association was observed with complexes constructed using 5 µg/mL of ATCOL. The complexes showed liposome concentration-dependent and time-dependent cellular association under a magnetic field, and their cellular uptake efficiency was comparable with that of Mag-CL. In addition, Mag-CL showed significant cytotoxicity in a liposome concentration-dependent manner, whereas Mag-AL/ATCOL complexes produced no cytotoxic effect against RAW264 cells. Furthermore, the efficient cellular association of Mag-AL/ATCOL complexes in RAW264 cells was observed even in the presence of serum, and their liver accumulation was significantly increased at a magnetic field-exposed region after intravenous injection in rats. These results indicate that Mag-AL/ATCOL complexes could be a safe and efficient magnetic responsive drug carrier.
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Affiliation(s)
- Yusuke Kono
- a Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences , Ritsumeikan University , Kusatsu , Japan.,b Ritsumeikan-Global Innovation Research Organization, Ritsumeikan University , Kusatsu , Japan
| | - Taketo Nakai
- a Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences , Ritsumeikan University , Kusatsu , Japan
| | - Hitomi Taguchi
- a Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences , Ritsumeikan University , Kusatsu , Japan
| | - Takuya Fujita
- a Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences , Ritsumeikan University , Kusatsu , Japan.,b Ritsumeikan-Global Innovation Research Organization, Ritsumeikan University , Kusatsu , Japan.,c Research Center for Drug Discovery and Development, Ritsumeikan University , Kusatsu , Japan
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46
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Riaz MK, Riaz MA, Zhang X, Lin C, Wong KH, Chen X, Zhang G, Lu A, Yang Z. Surface Functionalization and Targeting Strategies of Liposomes in Solid Tumor Therapy: A Review. Int J Mol Sci 2018; 19:E195. [PMID: 29315231 PMCID: PMC5796144 DOI: 10.3390/ijms19010195] [Citation(s) in RCA: 295] [Impact Index Per Article: 42.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 01/03/2018] [Accepted: 01/04/2018] [Indexed: 12/23/2022] Open
Abstract
Surface functionalization of liposomes can play a key role in overcoming the current limitations of nanocarriers to treat solid tumors, i.e., biological barriers and physiological factors. The phospholipid vesicles (liposomes) containing anticancer agents produce fewer side effects than non-liposomal anticancer formulations, and can effectively target the solid tumors. This article reviews information about the strategies for targeting of liposomes to solid tumors along with the possible targets in cancer cells, i.e., extracellular and intracellular targets and targets in tumor microenvironment or vasculature. Targeting ligands for functionalization of liposomes with relevant surface engineering techniques have been described. Stimuli strategies for enhanced delivery of anticancer agents at requisite location using stimuli-responsive functionalized liposomes have been discussed. Recent approaches for enhanced delivery of anticancer agents at tumor site with relevant surface functionalization techniques have been reviewed. Finally, current challenges of functionalized liposomes and future perspective of smart functionalized liposomes have been discussed.
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Affiliation(s)
- Muhammad Kashif Riaz
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Muhammad Adil Riaz
- School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, NSW 2006, Australia.
| | - Xue Zhang
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Congcong Lin
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Ka Hong Wong
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Xiaoyu Chen
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Ge Zhang
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Aiping Lu
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
| | - Zhijun Yang
- School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.
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47
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Moghimipour E, Rezaei M, Ramezani Z, Kouchak M, Amini M, Angali KA, Dorkoosh FA, Handali S. Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil. Eur J Pharm Sci 2017; 114:166-174. [PMID: 29247686 DOI: 10.1016/j.ejps.2017.12.011] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2017] [Revised: 12/11/2017] [Accepted: 12/12/2017] [Indexed: 01/02/2023]
Abstract
The aim of this study was to develop a liposomal formulation to selectively target cancer cells. Liposomes were prepared using thin layer method and folic acid (FA) was applied for targeted delivery of 5FU to cancer cells. Liposomes prepared were characterized for encapsulation efficiency (EE%), morphology and their particle size. Cellular uptake, cytotoxicity study and ROS production were evaluated using CT26 cell line. Hemolysis test was performed on rat red blood cells (RBCs). Moreover, the efficacy of targeted liposomes were investigated by in vivo antitumor activity and tissue toxicities were studied by histological examination. The EE% and average particle size of liposomes were 67.88±1.84% and 114.00±4.58nm, respectively. TEM image revealed that liposomes were spherical in shape. Targeted liposomes showed higher cellular uptake, lower IC50 (12.02μM compared to 39.81μM for liposomal 5FU and 39.81μM for free 5FU) and higher ROS production than free drug (62,271.28 vs 2369.55 fluorescence intensity) on cancer cells. Results of hemolysis assay confirmed the blood biocompatibility of the liposomes. Moreover, folate targeted liposomes showed better tumor inhibition than free drug (88.75mm3 tumor volume vs 210.00mm3) and no tissue abnormalities were found in histological examination. It can be concluded that folate targeted liposomes provide an effective and safe strategy for colon cancer targeted chemotherapy.
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Affiliation(s)
- Eskandar Moghimipour
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohsen Rezaei
- Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Zahra Ramezani
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Maryam Kouchak
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mohsen Amini
- Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Kambiz Ahmadi Angali
- Department of Biostatistics, School of Public Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Farid Abedin Dorkoosh
- Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran
| | - Somayeh Handali
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Kono Y, Jinzai H, Kotera Y, Fujita T. Influence of Physicochemical Properties and PEG Modification of Magnetic Liposomes on Their Interaction with Intestinal Epithelial Caco-2 Cells. Biol Pharm Bull 2017; 40:2166-2174. [PMID: 28966298 DOI: 10.1248/bpb.b17-00563] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The present study aimed to investigate the effect of particle size (100, 500 nm), surface charge (cationic, neutral and anionic) and polyethylene glycol (PEG) modification of magnetic liposomes on their interaction with the human intestinal epithelial cell line, Caco-2. The cellular associated amount of all the magnetic liposomes was significantly increased by the presence of a magnetic field. The highest association and internalization into Caco-2 cells was observed with magnetic cationic liposomes. Moreover, small magnetic liposomes were more efficiently associated and taken up into the cells, than large ones. In contrast, PEG modification significantly attenuated the enhancing effect of the magnetic field on the cellular association of magnetic liposomes. We also found that magnetic cationic liposomes had the highest retention properties to Caco-2 cells. Moreover, the retention of large magnetic liposomes to the cells was much longer than that of small ones. In addition, magnetic cationic and neutral liposomes had relatively high stability in Caco-2 cells, whereas magnetic anionic liposomes rapidly degraded. These results indicate that the physicochemical properties and PEG modification of magnetic liposomes greatly influences their intestinal epithelial transport.
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Affiliation(s)
- Yusuke Kono
- Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences, Ritsumeikan University.,Ritsumeikan-Global Innovation Research Organization, Ritsumeikan University
| | - Hitomi Jinzai
- Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences, Ritsumeikan University
| | - Yota Kotera
- Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences, Ritsumeikan University
| | - Takuya Fujita
- Laboratory of Molecular Pharmacokinetics, College of Pharmaceutical Sciences, Ritsumeikan University.,Ritsumeikan-Global Innovation Research Organization, Ritsumeikan University.,Research Center for Drug Discovery and Development, Ritsumeikan University
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Synthesis and Cytotoxicity of Arene-Ru Compounds Containing 4-Nitroaniline or 2-Halogenated 4-Nitroaniline. Z Anorg Allg Chem 2017. [DOI: 10.1002/zaac.201700154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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50
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Folic acid-decorated and PEGylated PLGA nanoparticles for improving the antitumour activity of 5-fluorouracil. Int J Pharm 2017; 516:61-70. [DOI: 10.1016/j.ijpharm.2016.11.012] [Citation(s) in RCA: 99] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2016] [Revised: 10/28/2016] [Accepted: 11/03/2016] [Indexed: 01/12/2023]
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