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Bao ZC, Liu ZD, Zhang Y, Dai HJ, Jia H, Ren F, Li N, Zhao L, Wang YW, Lv SY, Zhang Y. To investigate the effect and mechanism of tetrahydrocurcumin on hepatocellular carcinoma based on phosphoinositide 3-kinases/AKT signaling pathway. World J Gastrointest Oncol 2025; 17:102187. [PMID: 40092949 PMCID: PMC11866248 DOI: 10.4251/wjgo.v17.i3.102187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/20/2024] [Accepted: 01/02/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Liver cancer has a high incidence and mortality worldwide, especially in China. Herein, we investigated the therapeutic effect and mechanism of tetrahydrocurcumin against hepatocellular carcinoma (HCC), with a focus on the of phosphoinositide 3-kinases (PI3K)/AKT signaling pathway. AIM To investigate the effects and mechanism of tetrahydrocurcumin in HCC cell lines HepG2 and Huh7. METHODS Using Metascape, we analyzed the potential targets of tetrahydrocurcumin in HCC. Molecular docking validation was performed using SYBYL2.0. Cell Counting Kit-8, wound healing, and transwell assays were performed to evaluate the effects of tetrahydrocurcumin on HepG2 and Huh7 cell migration, invasion, and apoptosis. The expression of PI3K/AKT signaling pathway-related proteins was detected by western blotting. RESULTS Network pharmacology and molecular docking showed that tetrahydrocurcumin has high binding affinity for phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. In vitro experiments demonstrated that tetrahydrocurcumin suppressed the migration and invasion of liver cancer cells, promoted their apoptosis, and downregulated the expression of p-PI3K, p-AKT, and B cell leukemia/lymphoma 2, while upregulating caspase-3, p53, and B cell leukemia/lymphoma 2 associated X. CONCLUSION In summary, tetrahydrocurcumin suppresses PI3K/AKT signaling, promotes apoptosis, and prevents the migration and invasion of liver cancer cells.
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Affiliation(s)
- Zhuo-Cong Bao
- Graduate School, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Zhao-Dong Liu
- Graduate School, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Ye Zhang
- Graduate School, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Hui-Jun Dai
- Guangxi Medical University Cancer Hospital, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
| | - Hui Jia
- School of Traditional Chinese Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Fu Ren
- Key Laboratory of Human Ethnic Specificity and Phenomics of Critical Illness in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- Key Laboratory of Phenomics in Shenyang, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Ning Li
- Key Laboratory of Human Ethnic Specificity and Phenomics of Critical Illness in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- Key Laboratory of Phenomics in Shenyang, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- Department of Biochemistry, School of Basic Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Lu Zhao
- Department of Biochemistry, School of Basic Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Yi-Wei Wang
- Key Laboratory of Human Ethnic Specificity and Phenomics of Critical Illness in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- Molecular Morphology Laboratory, College of Basic Medical Sciences, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Shang-Yu Lv
- Batch 2022, Clinical Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
| | - Yan Zhang
- Key Laboratory of Human Ethnic Specificity and Phenomics of Critical Illness in Liaoning Province, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- Key Laboratory of Phenomics in Shenyang, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- Department of Biochemistry, School of Basic Medicine, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
- International Education School, International Exchange and Cooperation Office, Shenyang Medical College, Shenyang 110034, Liaoning Province, China
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Teerawonganan P, Hasriadi, Dasuni Wasana PW, Angsuwattana P, Suksamrarn A, Nalinratana N, Vajragupta O, Towiwat P, Thitikornpong W, Rojsitthisak P. Synthesis, Cytotoxicity, and Mechanistic Evaluation of Tetrahydrocurcumin-Amino Acid Conjugates as LAT1-Targeting Anticancer Agents in C6 Glioma Cells. Int J Mol Sci 2024; 25:11266. [PMID: 39457050 PMCID: PMC11509005 DOI: 10.3390/ijms252011266] [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] [Received: 09/12/2024] [Revised: 10/14/2024] [Accepted: 10/15/2024] [Indexed: 10/28/2024] Open
Abstract
Glioblastoma, a fatal brain cancer with limited treatments and poor prognosis, could benefit from targeting the L-type amino acid transporter I (LAT1). LAT1 is essential for cancer cells to acquire necessary amino acids. Tetrahydrocurcumin (THC), a key curcumin derivative, shows potential for glioblastoma treatment. However, its effectiveness is hindered by poor physicochemical and pharmacokinetic properties. Therefore, this study aims to improve the therapeutic efficacy of THC against glioblastoma by chemically modifying it to target LAT1. A novel series of THC-amino acid conjugates were synthesized by conjugating five amino acids: glycine, leucine, isoleucine, and phenylalanine to THC via carbamate bonds. The therapeutic efficacy of THC-amino acid conjugates was further examined in C6 glioma cells, including the role of LAT1 in their therapeutic effects. Among the conjugates tested, THC conjugated with two phenylalanines (THC-di-Phe) showed remarkably higher cytotoxicity against C6 glioma cells (35.8 μM) compared to THC alone (110.7 μM). THC-di-Phe induced cellular death via necrosis and apoptosis, outperforming THC. Additionally, THC-di-Phe inhibited C6 cell proliferation and migration more effectively than THC. Co-incubation of THC-di-Phe with the LAT1 inhibitor 2-Aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) further increased cellular death. THC-di-Phe also significantly inhibited the P70SK/S6 pathway, regulated by LAT1 inhibitors, more effectively than THC and displayed a similar binding mode with both JX-075 and BCH to the active site of LAT1. Findings suggest the potential role of THC-di-Phe as a LAT1 inhibitor and provide novel insight into its use as a potent antitumor agent in glioma with increased therapeutic efficacy.
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Affiliation(s)
- Polsak Teerawonganan
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Biomedicinal Chemistry Program, Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Hasriadi
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Peththa Wadu Dasuni Wasana
- Department of Pharmacy, Faculty of Allied Health Sciences, University of Ruhuna, Galle 80000, Sri Lanka;
| | - Pornpoom Angsuwattana
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;
| | - Apichart Suksamrarn
- Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand;
| | - Nonthaneth Nalinratana
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Opa Vajragupta
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Molecular Probes for Imaging Research Network, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Pasarapa Towiwat
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand
| | - Worathat Thitikornpong
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;
| | - Pornchai Rojsitthisak
- Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand; (P.T.); (H.); (N.N.); (O.V.); (P.T.); (W.T.)
- Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand;
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Zhang D, Liu L, Wang J, Zhang H, Zhang Z, Xing G, Wang X, Liu M. Drug-loaded PEG-PLGA nanoparticles for cancer treatment. Front Pharmacol 2022; 13:990505. [PMID: 36059964 PMCID: PMC9437283 DOI: 10.3389/fphar.2022.990505] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Accepted: 07/27/2022] [Indexed: 11/28/2022] Open
Abstract
Nanoparticles based on single-component synthetic polymers, such as poly (lactic acid-co-glycolic acid) (PLGA), have been extensively studied for antitumor drug delivery and adjuvant therapy due to their ability to encapsulate and release drugs, as well as passively target tumors. Amphiphilic block co-polymers, such as polyethylene glycol (PEG)-PLGA, have also been used to prepare multifunctional nanodrug delivery systems with prolonged circulation time and greater bioavailability that can encapsulate a wider variety of drugs, including small molecules, gene-targeting drugs, traditional Chinese medicine (TCM) and multi-target enzyme inhibitors, enhancing their antitumor effect and safety. In addition, the surface of PEG-PLGA nanoparticles has been modified with various ligands to achieve active targeting and selective accumulation of antitumor drugs in tumor cells. Modification with two ligands has also been applied with good antitumor effects, while the use of imaging agents and pH-responsive or magnetic materials has paved the way for the application of such nanoparticles in clinical diagnosis. In this work, we provide an overview of the synthesis and application of PEG-PLGA nanoparticles in cancer treatment and we discuss the recent advances in ligand modification for active tumor targeting.
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Affiliation(s)
- Dan Zhang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Pharmaceutical Department of Traditional Chinese Medicine, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Lin Liu
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jian Wang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Hong Zhang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhuo Zhang
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Gang Xing
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xuan Wang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- *Correspondence: Xuan Wang, ; Minghua Liu,
| | - Minghua Liu
- Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- *Correspondence: Xuan Wang, ; Minghua Liu,
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Madani F, Esnaashari SS, Webster TJ, Khosravani M, Adabi M. Polymeric nanoparticles for drug delivery in glioblastoma: State of the art and future perspectives. J Control Release 2022; 349:649-661. [PMID: 35878729 DOI: 10.1016/j.jconrel.2022.07.023] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Revised: 07/16/2022] [Accepted: 07/19/2022] [Indexed: 11/16/2022]
Abstract
Glioblastoma (GBM) is an aggressive, fatal and malignant primary brain tumor. Despite the current standard treatment for glioblastoma patients including neurosurgical resection, followed by concomitant radiation and chemotherapy, the median survival rate is only about 15 months. An unresolved challenge for current therapies is related to getting drugs through the blood-brain barrier (BBB), which hinders many chemotherapeutic agents from reaching tumors cells. Although a large amount of research has been done to circumvent the BBB and deliver drugs to the brain, with nanoparticles (NPs) taking the lead, the challenge is still high. In this regard, the BBB and how to transfer drug pathways through the BBB, especially using NPs, are introduced here. Afterwards, the latest advances in drug delivery, co-drug delivery, and combination modalities are described specifically for GBM treatments using natural and synthetic polymeric NPs and adjuvant therapies including hyperthermia, photodynamic therapy and also ketogenic regimens. In addition, receptor-mediated endocytosis agents that exist in endothelial capillary cells of the brain are explained. Lastly, future directions to finally deliver drugs through the BBB for GBM treatment are emphasized. It is the hope that this review can provide a number of practical pathways for the future development of BBB permeable nanochemotherapeutics against GBM.
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Affiliation(s)
- Fatemeh Madani
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Seyedeh Sara Esnaashari
- Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Thomas J Webster
- School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, China
| | - Masood Khosravani
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Mahdi Adabi
- Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran.
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Maleki Dizaj S, Salatin S, Khezri K, Lee JY, Lotfipour F. Targeting Multidrug Resistance With Antimicrobial Peptide-Decorated Nanoparticles and Polymers. Front Microbiol 2022; 13:831655. [PMID: 35432230 PMCID: PMC9009044 DOI: 10.3389/fmicb.2022.831655] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 03/09/2022] [Indexed: 01/21/2023] Open
Abstract
As a category of small peptides frequently found in nature, antimicrobial peptides (AMPs) constitute a major part of the innate immune system of various organisms. Antimicrobial peptides feature various inhibitory effects against fungi, bacteria, viruses, and parasites. Due to the increasing concerns of antibiotic resistance among microorganisms, development of antimicrobial peptides is an emerging tool as a favorable applicability prospect in food, medicine, aquaculture, animal husbandry, and agriculture. This review presents the latest research progress made in the field of antimicrobial peptides, such as their mechanism of action, classification, application status, design techniques, and a review on decoration of nanoparticles and polymers with AMPs that are used in treating multidrug resistance. Lastly, we will highlight recent progress in antiviral peptides to treat emerging viral diseases (e.g., anti-coronavirus peptides) and discuss the outlook of AMP applications.
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Affiliation(s)
- Solmaz Maleki Dizaj
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Dental Biomaterials, Faculty of Dentistry, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sara Salatin
- Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Khadijeh Khezri
- Deputy of Food and Drug Administration, Urmia University of Medical Sciences, Urmia, Iran
| | - Jyh-Yeuan Lee
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Farzaneh Lotfipour
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada
- Food and Drug Safety Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
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6
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Shahrad S, Rajabi M, Javadi H, Karimi Zarchi AA, Darvishi MH. Targeting lung cancer cells with MUC1 aptamer-functionalized PLA-PEG nanocarriers. Sci Rep 2022; 12:4718. [PMID: 35304550 PMCID: PMC8933396 DOI: 10.1038/s41598-022-08759-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 03/11/2022] [Indexed: 11/10/2022] Open
Abstract
MUC1 aptamer-functionalized PLA-PEG nanocarriers at various w/w ratios (polymer to doxorubicin weight ratio) were prepared by a double emulsion method. Physiochemical properties, encapsulation efficiency (EE), loading content (LC) and in vitro release kinetics of DOX were assessed. Furthermore, cytotoxicity and antitumor activity of prepared PLA-PEG-Apt/DOX NPs at w/w ratio 10:1 were evaluated by MTT assay and flow cytometry against MUC1-overexpressing A-549 cell line. Targeted nanocarriers (PLA-PEG-Apt/DOX NPs at w/w ratio 10:1) induced higher apoptosis rate (36.3 ± 3.44%) for 24 h in MUC1 positive A-549 cancer cells in compare to non-targeted form (PLA-PEG/DOX NPs at w/w ratio 10:1, 11.37 ± 1.65%) and free DOX (4.35 ± 0.81%). In other word, the percentage of cell death in A-549 lung cancer cells treated with PLA-PEG-Apt/DOX NPs at w/w ratio 10:1 is 3.19 and 8.34 fold higher than in non-targeted form and Free DOX treated cancer cells, respectively. Therefore, PLA-PEG-Apt/DOX NPs might be considered a promising drug delivery system for targeted drug delivery towards MUC1-overexpressing tumors cells.
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Affiliation(s)
- Shima Shahrad
- Department of Materials Engineering, Babol Noshirvani University of Technology, Shariati Ave., 47148-71167, Babol, Iran
| | - Mohammad Rajabi
- Department of Materials Engineering, Babol Noshirvani University of Technology, Shariati Ave., 47148-71167, Babol, Iran
| | - Hamidreza Javadi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Karimi Zarchi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Mohammad Hasan Darvishi
- Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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Ramalho MJ, Bravo M, Loureiro JA, Lima J, Pereira MC. Transferrin-modified nanoparticles for targeted delivery of Asiatic acid to glioblastoma cells. Life Sci 2022; 296:120435. [PMID: 35247437 DOI: 10.1016/j.lfs.2022.120435] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2021] [Revised: 02/14/2022] [Accepted: 02/22/2022] [Indexed: 01/16/2023]
Abstract
AIMS Glioblastoma (GBM) is the most common and deadliest type of brain cancer, and the current therapeutic options are not curative, imposing the need for novel strategies. Asiatic acid (AA) is a natural compound and has been explored due to its anti-glioma activity and lower toxicity to healthy tissues compared with conventional chemotherapeutic agents. However, its poor water-solubility is an obstacle for clinical application. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were proposed in this work for Asiatic acid (AA) delivery. MAIN METHODS A central composite design was implemented to optimize the NPs, and their surface was further modified with transferrin (Tf), for targeted delivery to GBM cells. The anti-glioma activity of the NPs was studied in vitro using human GBM cells and immortalized human astrocytes. KEY FINDINGS The NPs exhibited a mean size smaller than 200 nm, with low polydispersity and negative zeta potential, indicating their suitability for brain tumor delivery. The NPs also exhibited high encapsulation efficiency and maintained a slow and controlled release of AA for 20 days. In vitro cell studies showed that NPs were able to maintain the anti-glioma activity of the natural compound and that the surface modification with Tf molecules was able to increase the cellular uptake in GBM cells, enhancing their selectivity and decreasing toxicity in healthy cells. SIGNIFICANCE Overall, this work provided guidance for designing brain-targeting delivery systems of natural compounds.
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Affiliation(s)
- Maria João Ramalho
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
| | - Maria Bravo
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
| | - Joana Angélica Loureiro
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
| | - Jorge Lima
- i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen, 4200-10 135 Porto, Portugal.
| | - Maria Carmo Pereira
- LEPABE - Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal; ALiCE - Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal.
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Gomes ER, Franco MS. Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy. Pharmaceutics 2022; 14:pharmaceutics14010105. [PMID: 35057001 PMCID: PMC8781448 DOI: 10.3390/pharmaceutics14010105] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/23/2021] [Accepted: 12/29/2021] [Indexed: 12/12/2022] Open
Abstract
Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect.
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Affiliation(s)
- Eliza Rocha Gomes
- Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil;
| | - Marina Santiago Franco
- Department of Radiation Sciences (DRS), Institute of Radiation Medicine (IRM), 85764 München, Germany
- Correspondence: ; Tel.: +49-89-3187-48767
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Ostrowski RP, He Z, Pucko EB, Matyja E. Hemorrhage in brain tumor – An unresolved issue. BRAIN HEMORRHAGES 2022. [DOI: 10.1016/j.hest.2022.01.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
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10
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Liu W, Chen B, Zheng H, Xing Y, Chen G, Zhou P, Qian L, Min Y. Advances of Nanomedicine in Radiotherapy. Pharmaceutics 2021; 13:pharmaceutics13111757. [PMID: 34834172 PMCID: PMC8622383 DOI: 10.3390/pharmaceutics13111757] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/28/2021] [Accepted: 10/08/2021] [Indexed: 12/14/2022] Open
Abstract
Radiotherapy (RT) remains one of the current main treatment strategies for many types of cancer. However, how to improve RT efficiency while reducing its side effects is still a large challenge to be overcome. Advancements in nanomedicine have provided many effective approaches for radiosensitization. Metal nanoparticles (NPs) such as platinum-based or hafnium-based NPs are proved to be ideal radiosensitizers because of their unique physicochemical properties and high X-ray absorption efficiency. With nanoparticles, such as liposomes, bovine serum albumin, and polymers, the radiosensitizing drugs can be promoted to reach the tumor sites, thereby enhancing anti-tumor responses. Nowadays, the combination of some NPs and RT have been applied to clinical treatment for many types of cancer, including breast cancer. Here, as well as reviewing recent studies on radiotherapy combined with inorganic, organic, and biomimetic nanomaterials for oncology, we analyzed the underlying mechanisms of NPs radiosensitization, which may contribute to exploring new directions for the clinical translation of nanoparticle-based radiosensitizers.
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Affiliation(s)
- Wei Liu
- Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; (W.L.); (P.Z.)
| | - Bo Chen
- Department of Bio-X Interdisciplinary Science at Hefei National Laboratory (HFNL) for Physical Science at the Microscale, University of Science and Technology of China, Hefei 230026, China; (B.C.); (Y.M.)
| | - Haocheng Zheng
- Department of Endocrinology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (H.Z.); (Y.X.); (G.C.)
- CAS Key Lab of Soft Matter Chemistry, University of Science and Technology of China, Hefei 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
| | - Yun Xing
- Department of Endocrinology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (H.Z.); (Y.X.); (G.C.)
- CAS Key Lab of Soft Matter Chemistry, University of Science and Technology of China, Hefei 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
| | - Guiyuan Chen
- Department of Endocrinology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (H.Z.); (Y.X.); (G.C.)
- CAS Key Lab of Soft Matter Chemistry, University of Science and Technology of China, Hefei 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
| | - Peijie Zhou
- Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; (W.L.); (P.Z.)
| | - Liting Qian
- Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China; (W.L.); (P.Z.)
- Correspondence:
| | - Yuanzeng Min
- Department of Bio-X Interdisciplinary Science at Hefei National Laboratory (HFNL) for Physical Science at the Microscale, University of Science and Technology of China, Hefei 230026, China; (B.C.); (Y.M.)
- Department of Endocrinology, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China; (H.Z.); (Y.X.); (G.C.)
- CAS Key Lab of Soft Matter Chemistry, University of Science and Technology of China, Hefei 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei 230026, China
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11
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Li S, Guo J, Tian Z, Chen J, Gou G, Niu Y, Li L, Yang J. Piperine-Loaded Glycyrrhizic Acid- and PLGA-Based Nanoparticles Modified with Transferrin for Antitumor : Piperine-Loaded Glycyrrhizic Acid- and PLGA-Based Nanoparticles. AAPS PharmSciTech 2021; 22:239. [PMID: 34590204 DOI: 10.1208/s12249-021-02123-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 08/18/2021] [Indexed: 12/13/2022] Open
Abstract
The purpose of this study was to enhance the antitumor effect of piperine by constructing the nanoparticles modified with transferrin (Tf-PIP-NPs) and evaluating their efficacy in vitro and in vivo. The Tf-PIP-NPs were prepared by the solvent evaporation method, and their properties were characterized. The effects of Tf-PIP-NPs on cytotoxicity, cell uptake, apoptosis, and mitochondrial membrane potential were evaluated in HepG2 cells, MDA-MB-231 cells, and 4T1 cells. In a 4T1 tumor-bearing mouse model, the antitumor efficacy of Tf-PIP-NPs was assessed in terms of tumor volumes, changes in body weight, HE staining, and immunohistochemical analysis. With a mean particle size of 112.2 ± 1.27 nm, the zeta potential of (- 28.0 ± 1.6 mV) Tf-PIP-NPs were rapidly internalized by tumor cells after 1 h through the transferrin receptor (TfR)-mediated endocytosis pathway, significantly inducing cellular apoptosis and mitochondrial membrane potential loss. Although Tf-PIP-NPs had no significant difference with PIP-NPs in tumor volume inhibition due to the presence of tumor microenvironment, it could significantly upregulate the expression of related pro-apoptotic proteins and induce tumor necrosis. We used the self-assembly properties of glycyrrhizic acid (GL) and polymer-PLGA to encapsulate piperine and modified with the transferrin, which provided a promising approach to improve the antitumor efficacy for anticarcinogen.
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12
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Scheeren LE, Nogueira-Librelotto DR, Mathes D, Pillat MM, Macedo LB, Mitjans M, Vinardell MP, Rolim CMB. Multifunctional PLGA nanoparticles combining transferrin-targetability and pH-stimuli sensitivity enhanced doxorubicin intracellular delivery and in vitro antineoplastic activity in MDR tumor cells. Toxicol In Vitro 2021; 75:105192. [PMID: 33984456 DOI: 10.1016/j.tiv.2021.105192] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 04/22/2021] [Accepted: 05/09/2021] [Indexed: 11/29/2022]
Abstract
Targeted delivery aims to enhance cellular uptake and improve therapeutic outcome with higher disease specificity. The expression of transferrin receptor (TfR) is upregulated on tumor cells, which make the protein Tf and its receptor vastly relevant when applied to targeting strategies. Here, we proposed Tf-decorated pH-sensitive PLGA nanoparticles containing the chemosensitizer poloxamer as a carrier for doxorubicin delivery to tumor cells (Tf-DOX-PLGA-NPs), aiming at alleviating multidrug resistance (MDR). We performed a range of in vitro studies to assess whether targeted NPs have the ability to improve DOX antitumor potential on resistant NCI/ADR-RES cells. All evaluations of the Tf-decorated NPs were performed comparatively to the nontargeted counterparts, aiming to evidence the real role of NP surface functionalization, along with the benefits of pH-sensitivity and poloxamer, in the improvement of antiproliferative activity and reversal of MDR. Tf-DOX-PLGA-NPs induced higher number of apoptotic events and ROS generation, along with cell cycle arrest. Moreover, they were efficiently internalized by NCI/ADR-RES cells, increasing DOX intracellular accumulation, which supports the greater cell killing ability of these targeted NPs with respect to MDR cells. Altogether, these findings supported the effectiveness of the Tf-surface modification of DOX-PLGA-NPs for an improved antiproliferative activity. Therefore, our pH-responsive Tf-inspired NPs are a promising smart drug delivery system to overcome MDR effect at some extent, enhancing the efficacy of DOX antitumor therapy.
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Affiliation(s)
- Laís E Scheeren
- Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil
| | - Daniele R Nogueira-Librelotto
- Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil.
| | - Daniela Mathes
- Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil
| | - Micheli M Pillat
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Departamento de Microbiologia e Parasitologia, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil
| | - Letícia B Macedo
- Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil
| | - Montserrat Mitjans
- Departament de Bioquimica i Fisiologia, Facultat de Farmacia i Ciències de l'Alimentació, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain
| | - M Pilar Vinardell
- Departament de Bioquimica i Fisiologia, Facultat de Farmacia i Ciències de l'Alimentació, Universitat de Barcelona, Av. Joan XXIII 27-31, 08028 Barcelona, Spain
| | - Clarice M B Rolim
- Departamento de Farmácia Industrial, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Santa Maria, Av. Roraima 1000, 97105-900 Santa Maria, RS, Brazil.
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13
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Zhi K, Raji B, Nookala AR, Khan MM, Nguyen XH, Sakshi S, Pourmotabbed T, Yallapu MM, Kochat H, Tadrous E, Pernell S, Kumar S. PLGA Nanoparticle-Based Formulations to Cross the Blood-Brain Barrier for Drug Delivery: From R&D to cGMP. Pharmaceutics 2021; 13:pharmaceutics13040500. [PMID: 33917577 PMCID: PMC8067506 DOI: 10.3390/pharmaceutics13040500] [Citation(s) in RCA: 68] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 04/03/2021] [Accepted: 04/05/2021] [Indexed: 12/24/2022] Open
Abstract
The blood–brain barrier (BBB) is a natural obstacle for drug delivery into the human brain, hindering treatment of central nervous system (CNS) disorders such as acute ischemic stroke, brain tumors, and human immunodeficiency virus (HIV)-1-associated neurocognitive disorders. Poly(lactic-co-glycolic acid) (PLGA) is a biocompatible polymer that is used in Food and Drug Administration (FDA)-approved pharmaceutical products and medical devices. PLGA nanoparticles (NPs) have been reported to improve drug penetration across the BBB both in vitro and in vivo. Poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), and poloxamer (Pluronic) are widely used as excipients to further improve the stability and effectiveness of PLGA formulations. Peptides and other linkers can be attached on the surface of PLGA to provide targeting delivery. With the newly published guidance from the FDA and the progress of current Good Manufacturing Practice (cGMP) technologies, manufacturing PLGA NP-based drug products can be achieved with higher efficiency, larger quantity, and better quality. The translation from bench to bed is feasible with proper research, concurrent development, quality control, and regulatory assurance.
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Affiliation(s)
- Kaining Zhi
- Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA; (B.R.); (H.K.)
- Correspondence: (K.Z.); (S.K.)
| | - Babatunde Raji
- Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA; (B.R.); (H.K.)
| | | | - Mohammad Moshahid Khan
- Department of Neurology, College of Medicine, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN 38163, USA;
| | - Xuyen H. Nguyen
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA; (X.H.N.); (S.S.); (E.T.); (S.P.)
| | - Swarna Sakshi
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA; (X.H.N.); (S.S.); (E.T.); (S.P.)
| | - Tayebeh Pourmotabbed
- Department of Microbiology, Immunology and Biochemistry, College of Medicine, University of Tennessee Health Science Center, 858 Madison Avenue, Memphis, TN 38163, USA;
| | - Murali M. Yallapu
- Department of Immunology and Microbiology, University of Texas Rio Grande Valley, McAllen, TX 78504, USA;
| | - Harry Kochat
- Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, 208 South Dudley Street, Memphis, TN 38163, USA; (B.R.); (H.K.)
| | - Erene Tadrous
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA; (X.H.N.); (S.S.); (E.T.); (S.P.)
| | - Shelby Pernell
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA; (X.H.N.); (S.S.); (E.T.); (S.P.)
| | - Santosh Kumar
- Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, 881 Madison Ave, Memphis, TN 38163, USA; (X.H.N.); (S.S.); (E.T.); (S.P.)
- Correspondence: (K.Z.); (S.K.)
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14
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Synergetic therapy of glioma mediated by a dual delivery system loading α-mangostin and doxorubicin through cell cycle arrest and apoptotic pathways. Cell Death Dis 2020; 11:928. [PMID: 33116114 PMCID: PMC7595144 DOI: 10.1038/s41419-020-03133-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 10/04/2020] [Accepted: 10/06/2020] [Indexed: 02/05/2023]
Abstract
Two of the biggest hurdles in the deployment of chemotherapeutics against glioma is a poor drug concentration at the tumor site and serious side effects to normal tissues. Nanocarriers delivering different drugs are considered to be one of the most promising alternatives. In this study, a dual delivery system (methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL)) loaded with α-mangostin (α-m) and doxorubicin (Dox) was decorated and constructed by self-assembly to determine its ability to treat glioma. Molecular dynamics simulations showed that MPEG-PCL could provide ideal interaction positions for both α-m and Dox, indicating that the two drugs could be loaded into MPEG-PCL. Based on the in vitro results, MPEG-PCL loaded with α-m and Dox (α-m-Dox/M) with a size of 25.68 nm and a potential of -1.51 mV was demonstrated to significantly inhibit the growth and promote apoptosis in Gl261, C6 and U87 cells, and the effects of the combination were better than each compound alone. The mechanisms involved in the suppression of glioma cell growth were blockage of the cell cycle in S phase by inhibition of CDK2/cyclin E1 and promotion of apoptosis through the Bcl-2/Bax pathway. The synergetic effects of α-m-Dox/M effectively inhibited tumor growth and prolonged survival time without toxicity in mouse glioma models by inducing glioma apoptosis, inhibiting glioma proliferation and limiting tumor angiogenesis. In conclusion, a codelivery system was synthesized to deliver α-m and Dox to the glioma, thereby suppressing the development of glioma by the mechanisms of cell cycle arrest and cellular apoptosis, which demonstrated the potential of this system to improve the chemotherapy response of glioma.
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15
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Zhang X, Zhao L, Zhai G, Ji J, Liu A. Erratum: Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma. MEDICAL SCIENCE MONITOR : INTERNATIONAL MEDICAL JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2020; 26:e926333. [PMID: 32530909 PMCID: PMC7307716 DOI: 10.12659/msm.926333] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Xingzhen Zhang
- Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland).,Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong, China (mainland)
| | - Lixia Zhao
- Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland).,Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong, China (mainland)
| | - Guangxi Zhai
- Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong, China (mainland)
| | - Jianbo Ji
- Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong, China (mainland)
| | - Anchang Liu
- Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland).,Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong, China (mainland)
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16
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Lai CS, Ho CT, Pan MH. The Cancer Chemopreventive and Therapeutic Potential of Tetrahydrocurcumin. Biomolecules 2020; 10:E831. [PMID: 32486019 PMCID: PMC7356876 DOI: 10.3390/biom10060831] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/20/2020] [Accepted: 05/21/2020] [Indexed: 12/12/2022] Open
Abstract
In recent decades, cancer has been one of the leading causes of death worldwide. Despite advances in understanding the molecular basis of tumorigenesis, diagnosis, and clinical therapies, the discovery and development of effective drugs is an active and vital field in cancer research. Tetrahydrocurcumin is a major curcuminoid metabolite of curcumin, naturally occurring in turmeric. The interest in tetrahydrocurcumin research is increasing because it is superior to curcumin in its solubility in water, chemical stability, bioavailability, and anti-oxidative activity. Many in vitro and in vivo studies have revealed that tetrahydrocurcumin exerts anti-cancer effects through various mechanisms, including modulation of oxidative stress, xenobiotic detoxification, inflammation, proliferation, metastasis, programmed cell death, and immunity. Despite the pharmacological similarities between tetrahydrocurcumin and curcumin, the structure of tetrahydrocurcumin determines its distinct and specific molecular mechanism, thus making it a potential candidate for the prevention and treatment of cancers. However, the utility of tetrahydrocurcumin is yet to be evaluated as only limited pharmacokinetic and oral bioavailability studies have been performed. This review summarizes research on the anti-cancer properties of tetrahydrocurcumin and describes its mechanisms of action.
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Affiliation(s)
- Ching-Shu Lai
- Department of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, Taiwan;
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ 08901, USA;
| | - Min-Hsiung Pan
- Institute of Food Science and Technology, National Taiwan University, Taipei 10617, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan
- Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan
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17
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Fraguas-Sánchez AI, Torres-Suárez AI, Cohen M, Delie F, Bastida-Ruiz D, Yart L, Martin-Sabroso C, Fernández-Carballido A. PLGA Nanoparticles for the Intraperitoneal Administration of CBD in the Treatment of Ovarian Cancer: In Vitro and In Ovo Assessment. Pharmaceutics 2020; 12:pharmaceutics12050439. [PMID: 32397428 PMCID: PMC7285054 DOI: 10.3390/pharmaceutics12050439] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 05/06/2020] [Accepted: 05/07/2020] [Indexed: 12/18/2022] Open
Abstract
The intraperitoneal administration of chemotherapeutics has emerged as a potential route in ovarian cancer treatment. Nanoparticles as carriers for these agents could be interesting by increasing the retention of chemotherapeutics within the peritoneal cavity. Moreover, nanoparticles could be internalised by cancer cells and let the drug release near the biological target, which could increase the anticancer efficacy. Cannabidiol (CBD), the main nonpsychotropic cannabinoid, appears as a potential anticancer drug. The aim of this work was to develop polymer nanoparticles as CBD carriers capable of being internalised by ovarian cancer cells. The drug-loaded nanoparticles (CBD-NPs) exhibited a spherical shape, a particle size around 240 nm and a negative zeta potential (-16.6 ± 1.2 mV). The encapsulation efficiency was high, with values above 95%. A controlled CBD release for 96 h was achieved. Nanoparticle internalisation in SKOV-3 epithelial ovarian cancer cells mainly occurred between 2 and 4 h of incubation. CBD antiproliferative activity in ovarian cancer cells was preserved after encapsulation. In fact, CBD-NPs showed a lower IC50 values than CBD in solution. Both CBD in solution and CBD-NPs induced the expression of PARP, indicating the onset of apoptosis. In SKOV-3-derived tumours formed in the chick embryo model, a slightly higher-although not statistically significant-tumour growth inhibition was observed with CBD-NPs compared to CBD in solution. To sum up, poly-lactic-co-glycolic acid (PLGA) nanoparticles could be a good strategy to deliver CBD intraperitoneally for ovarian cancer treatment.
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Affiliation(s)
- Ana I. Fraguas-Sánchez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, Spain; (A.I.F.-S.); (A.I.T.-S.); (C.M.-S.)
| | - Ana I. Torres-Suárez
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, Spain; (A.I.F.-S.); (A.I.T.-S.); (C.M.-S.)
- Institute of Industrial Pharmacy, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Marie Cohen
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland; (M.C.); (D.B.-R.); (L.Y.)
| | - Florence Delie
- School of Pharmaceutical Sciences, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland;
| | - Daniel Bastida-Ruiz
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland; (M.C.); (D.B.-R.); (L.Y.)
| | - Lucile Yart
- Department of Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, Rue Michel-Servet 1, 1211 Geneva, Switzerland; (M.C.); (D.B.-R.); (L.Y.)
| | - Cristina Martin-Sabroso
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, Spain; (A.I.F.-S.); (A.I.T.-S.); (C.M.-S.)
- Institute of Industrial Pharmacy, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Ana Fernández-Carballido
- Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., 28040 Madrid, Spain; (A.I.F.-S.); (A.I.T.-S.); (C.M.-S.)
- Institute of Industrial Pharmacy, Faculty of Pharmacy, Complutense University of Madrid, Pl Ramón y Cajal s/n., Universidad Complutense de Madrid, 28040 Madrid, Spain
- Correspondence: ; Tel.: +34-913941741
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