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Tan YF, Hii LW, Lim WM, Cheong SK, Leong CO, Yee MSL, Mai CW. Polyethylene glycol-phospholipid functionalized single-walled carbon nanotubes for enhanced siRNA systemic delivery. Sci Rep 2024; 14:30098. [PMID: 39627280 PMCID: PMC11615393 DOI: 10.1038/s41598-024-80646-1] [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: 08/05/2024] [Accepted: 11/21/2024] [Indexed: 12/06/2024] Open
Abstract
Small interfering RNAs (siRNA) technology has emerged as a promising therapeutic tool for human health conditions like cancer due to its ability to regulate gene silencing. Despite FDA-approved, their delivery remains localized and limiting their systemic use. This study used single-walled carbon nanotubes (SWNTs) functionalized with polyethylene glycolated (PEGylated) phospholipids (PL-PEG) derivatives for systemic siRNA delivery. We developed an siRNA systemic delivery vehicle (SWNT-siRNA) by conjugating SWNT functionalized with PL-PEG containing either amine (PA) or maleimide (MA). The functionalized SWNT with a lower molecular weight of PA produced the SWNT-siRNA conjugate system with the highest stability and high siRNA loading quantity. The system delivered siRNA to a panel of tumour cell lines of different organs (i.e. HeLa, H1299 and MCF-7) and a non-cancerous human embryonic kidney 293 cells (HEK293T) with high biocompatibility and low toxicity. The cellular uptake of SWNT-siRNA conjugates by epithelial cells was found to be energy dependent. Importantly, the presence of P-glycoprotein, a marker for drug resistance, did not inhibit SWNT-mediated siRNA delivery. Mouse xenograft model further confirmed the potential of SWNT-siRNA conjugates with a significant gene knock-down without signs of acute toxicity. These findings pave the way for potential gene therapy applications using SWNTs as delivery vehicles.
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Affiliation(s)
- Yuen-Fen Tan
- Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia
- School of Postgraduate Studies, IMU University, Kuala Lumpur, 57000, Malaysia
- Cytovision Sdn. Bhd, Kuala Lumpur, 57000, Malaysia
| | - Ling-Wei Hii
- Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia
| | - Wei-Meng Lim
- Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia
- School of Pharmacy, Monash University Malaysia, Shah Alam, 47500, Selangor, Malaysia
| | - Soon-Keng Cheong
- Centre for Stem Cell Research, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Shah Alam, 43000, Selangor, Malaysia
| | - Chee-Onn Leong
- Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia
- School of Pharmacy, IMU University, Kuala Lumpur, 57000, Malaysia
- AGTC Genomics Sdn. Bhd, Kuala Lumpur, 57000, Malaysia
| | - Maxine Swee-Li Yee
- Nanotechnology Research Group, Center for Nanotechnology and Advanced Materials, University of Nottingham Malaysia, Semenyih, 43500, Selangor, Malaysia.
| | - Chun-Wai Mai
- Centre for Cancer and Stem Cell Research, Institute for Research, Development and Innovation (IRDI), IMU University, Kuala Lumpur, 57000, Malaysia.
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, 56000, Malaysia.
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Saadh MJ, Mustafa MA, Kumar S, Gupta P, Pramanik A, Rizaev JA, Shareef HK, Alubiady MHS, Al-Abdeen SHZ, Shakier HG, Alaraj M, Alzubaidi LH. Advancing therapeutic efficacy: nanovesicular delivery systems for medicinal plant-based therapeutics. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:7229-7254. [PMID: 38700796 DOI: 10.1007/s00210-024-03104-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 04/12/2024] [Indexed: 10/04/2024]
Abstract
The utilization of medicinal plant extracts in therapeutics has been hindered by various challenges, including poor bioavailability and stability issues. Nanovesicular delivery systems have emerged as promising tools to overcome these limitations by enhancing the solubility, bioavailability, and targeted delivery of bioactive compounds from medicinal plants. This review explores the applications of nanovesicular delivery systems in antibacterial and anticancer therapeutics using medicinal plant extracts. We provide an overview of the bioactive compounds present in medicinal plants and their therapeutic properties, emphasizing the challenges associated with their utilization. Various types of nanovesicular delivery systems, including liposomes, niosomes, ethosomes, and solid lipid nanoparticles, among others, are discussed in detail, along with their potential applications in combating bacterial infections and cancer. The review highlights specific examples of antibacterial and anticancer activities demonstrated by these delivery systems against a range of pathogens and cancer types. Furthermore, we address the challenges and limitations associated with the scale-up, stability, toxicity, and regulatory considerations of nanovesicular delivery systems. Finally, future perspectives are outlined, focusing on emerging technologies, integration with personalized medicine, and potential collaborations to drive forward research in this field. Overall, this review underscores the potential of nanovesicular delivery systems for enhancing the therapeutic efficacy of medicinal plant extracts in antibacterial and anticancer applications, while identifying avenues for further research and development.
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Affiliation(s)
- Mohamed J Saadh
- Faculty of Pharmacy, Middle East University, Amman, 11831, Jordan.
| | - Mohammed Ahmed Mustafa
- Department of Medical Laboratory Technology, University of Imam Jaafar AL-Sadiq, Baghdad, Iraq
| | - Sanjay Kumar
- Department of Biotechnology and Genetics, Jain (Deemed-to-Be) University, Bengaluru, Karnataka, 560069, India
- Department of Allied Healthcare and Sciences, Vivekananda Global University, Jaipur, Rajasthan, 303012, India
| | - Pooja Gupta
- School of Basic & Applied Sciences, Shobhit University, Gangoh, Uttar Pradesh, 247341, India
- Department of Health & Allied Sciences, Arka Jain University, Jamshedpur, Jharkhand, 831001, India
| | - Atreyi Pramanik
- School of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Jasur Alimdjanovich Rizaev
- Department of Public Health and Healthcare Management, Samarkand State Medical University, 18, Amir Temur Street, Rector, Samarkand, Uzbekistan
| | - Hasanain Khaleel Shareef
- Department of Medical Biotechnology, College of Science, Al-Mustaqbal University, Hilla, Iraq
- Biology Department, College of Science for Women, University of Babylon, Hilla, Iraq
| | | | | | | | - Mohd Alaraj
- Faculty of Pharmacy, Jerash Private University, Jerash, Jordan
| | - Laith H Alzubaidi
- College of Technical Engineering, The Islamic University, Najaf, Iraq
- College of Technical Engineering, The Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq
- College of Technical Engineering, The Islamic University of Babylon, Babylon, Iraq
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Roostaee M, Derakhshani A, Mirhosseini H, Banaee Mofakham E, Fathi-Karkan S, Mirinejad S, Sargazi S, Barani M. Composition, preparation methods, and applications of nanoniosomes as codelivery systems: a review of emerging therapies with emphasis on cancer. NANOSCALE 2024; 16:2713-2746. [PMID: 38213285 DOI: 10.1039/d3nr03495j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
Nanoniosome-based drug codelivery systems have become popular therapeutic instruments, demonstrating tremendous promise in cancer therapy, infection treatment, and other therapeutic domains. An emerging form of vesicular nanocarriers, niosomes are self-assembling vesicles composed of nonionic surfactants, along with cholesterol or other amphiphilic molecules. This comprehensive review focuses on how nanosystems may aid in making anticancer and antibacterial pharmaceuticals more stable and soluble. As malleable nanodelivery instruments, the composition, types, preparation procedures, and variables affecting the structure and stability of niosomes are extensively investigated. In addition, the advantages of dual niosomes for combination therapy and the administration of multiple medications simultaneously are highlighted. Along with categorizing niosomal drug delivery systems, a comprehensive analysis of various preparation techniques, including thin-layer injection, ether injection, and microfluidization, is provided. Dual niosomes for cancer treatment are discussed in detail regarding the codelivery of two medications and the codelivery of a drug with organic, plant-based bioactive compounds or gene agents. In addition, niogelosomes and metallic niosomal carriers for targeted distribution are discussed. The review also investigates the simultaneous delivery of bioactive substances and gene agents, including siRNA, microRNA, shRNA, lncRNA, and DNA. Additional sections discuss the use of dual niosomes for cutaneous drug delivery and treating leishmanial infections, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The study concludes by delineating the challenges and potential routes for nanoniosome-based pharmaceutical codelivery systems, which will be useful for nanomedicine practitioners and researchers.
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Affiliation(s)
- Maryam Roostaee
- Department of Chemistry, Faculty of Sciences, Vali-e-Asr University of Rafsanjan, Rafsanjan, Iran.
| | - Atefeh Derakhshani
- Department of Tissue Engineering, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
| | - Hadiseh Mirhosseini
- Department of Chemistry, Faculty of Sciences, Shahid Bahonar University of Kerman, Kerman, Iran.
| | - Elmira Banaee Mofakham
- Department of Nanotechnology and Advanced Materials Research, Materials & Energy Research Center, Karaj, Iran.
| | - Sonia Fathi-Karkan
- Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, 94531-55166, Iran.
- Department of Advanced Sciences and Technologies in Medicine, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd 9414974877, Iran.
| | - Shekoufeh Mirinejad
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
| | - Saman Sargazi
- Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran.
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mahmood Barani
- Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences, Kerman 7616913555, Iran.
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Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, Akbarzadeh I, Abtahi MS, Hejabi F, Ren Q. Current advances in niosomes applications for drug delivery and cancer treatment. Mater Today Bio 2023; 23:100837. [PMID: 37953758 PMCID: PMC10632535 DOI: 10.1016/j.mtbio.2023.100837] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 09/21/2023] [Accepted: 10/16/2023] [Indexed: 11/14/2023] Open
Abstract
The advent of nanotechnology has led to an increased interest in nanocarriers as a drug delivery system that is efficient and safe. There have been many studies addressing nano-scale vesicular systems such as liposomes and niosome is a newer generation of vesicular nanocarriers. The niosomes provide a multilamellar carrier for lipophilic and hydrophilic bioactive substances in the self-assembled vesicle, which are composed of non-ionic surfactants in conjunction with cholesterol or other amphiphilic molecules. These non-ionic surfactant vesicles, simply known as niosomes, can be utilized in a wide variety of technological applications. As an alternative to liposomes, niosomes are considered more chemically and physically stable. The methods for preparing niosomes are more economic. Many reports have discussed niosomes in terms of their physicochemical properties and applications as drug delivery systems. As drug carriers, nano-sized niosomes expand the horizons of pharmacokinetics, decreasing toxicity, enhancing drug solvability and bioavailability. In this review, we review the components and fabrication methods of niosomes, as well as their functionalization, characterization, administration routes, and applications in cancer gene delivery, and natural product delivery. We also discuss the limitations and challenges in the development of niosomes, and provide the future perspective of niosomes.
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Affiliation(s)
- Ali Moammeri
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | | | - Hamidreza Sahrayi
- Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran
| | | | - Farkhondeh Memarzadeh
- Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran
| | - Afsoun Mansouri
- School of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Iman Akbarzadeh
- Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran
| | - Maryam Sadat Abtahi
- School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Faranak Hejabi
- Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
| | - Qun Ren
- Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, 9014, St. Gallen, Switzerland
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5
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Fu JY, Meganathan P, Gunasegaran N, Tan DMY. Effect of nano-delivery systems on the bioavailability and tissue biodistribution of vitamin E tocotrienols. Food Res Int 2023; 171:113048. [PMID: 37330852 DOI: 10.1016/j.foodres.2023.113048] [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: 11/27/2022] [Revised: 05/22/2023] [Accepted: 05/23/2023] [Indexed: 06/19/2023]
Abstract
Vitamin E is one of the most important essential vitamins to support the regulation of oxidative stress in human body. Tocotrienols are part of the vitamin E family. The potentials of tocotrienols as nutraceutical ingredient are largely understated due to low oral bioavailability, which is a common problem associated with fat-soluble bioactive compounds. Nanoencapsulation technology offers innovative solutions to enhance the delivery mechanisms of these compounds. In this study, the effect of nanoencapsulation on the oral bioavailability and tissue distribution of tocotrienols were investigated using two types of formulations, i.e. nanovesicles (NV-T3) and solid lipid nanoparticles (NP-T3). At least 5-fold increment in maximum plasma concentrations, evident with dual-peak pharmacokinetic profiles, were observed after oral administration of nano-encapsulated tocotrienols. Plasma tocotrienol composition showed a shift from α-tocotrienol dominant in control group (Control-T3) to γ-tocotrienol dominant after nanoencapsulation. Tissue distribution of tocotrienols was found to be strongly influenced by the type of nanoformulation. Both nanovesicles (NV-T3) and nanoparticles (NP-T3) showed elevated accumulation in the kidneys and liver (5-fold) compared to control group while selectivity for α-tocotrienol was evident for NP-T3. In brain and liver of rats given NP-T3, α-tocotrienol emerged as the dominant congener (>80%). Acute oral administration of nanoencapsulated tocotrienols did not show signs of toxicity. The study concluded enhanced bioavailability and selective tissue accumulation of tocotrienol congeners when delivered via nanoencapsulation.
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Affiliation(s)
- Ju-Yen Fu
- Product Development and Advisory Department, Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia.
| | - Puvaneswari Meganathan
- Product Development and Advisory Department, Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia; Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
| | - Nisanthei Gunasegaran
- Product Development and Advisory Department, Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia; School of Pharmacy, International Medical University, 126, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur, Malaysia
| | - Doryn Meam Yee Tan
- Product Development and Advisory Department, Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 43000 Kajang, Selangor, Malaysia; School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500 Selangor, Malaysia
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6
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Ekeuku SO, Etim EP, Pang KL, Chin KY, Mai CW. Vitamin E in the management of pancreatic cancer: A scoping review. World J Gastrointest Oncol 2023; 15:943-958. [PMID: 37389119 PMCID: PMC10302993 DOI: 10.4251/wjgo.v15.i6.943] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Revised: 02/03/2023] [Accepted: 04/07/2023] [Indexed: 06/14/2023] Open
Abstract
Pancreatic cancer is the leading cause of cancer mortality worldwide. Research investigating effective management strategies for pancreatic cancer is ongoing. Vitamin E, consisting of both tocopherol and tocotrienol, has demonstrated debatable effects on pancreatic cancer cells. Therefore, this scoping review aims to summarize the effects of vitamin E on pancreatic cancer. In October 2022, a literature search was conducted using PubMed and Scopus since their inception. Original studies on the effects of vitamin E on pancreatic cancer, including cell cultures, animal models and human clinical trials, were considered for this review. The literature search found 75 articles on this topic, but only 24 articles met the inclusion criteria. The available evidence showed that vitamin E modulated proliferation, cell death, angiogenesis, metastasis and inflammation in pancreatic cancer cells. However, the safety and bioavailability concerns remain to be answered with more extensive preclinical and clinical studies. More in-depth analysis is necessary to investigate further the role of vitamin E in the management of pancreatic cancers.
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Affiliation(s)
- Sophia Ogechi Ekeuku
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Effiong Paul Etim
- Faculty of Applied Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
| | - Kok-Lun Pang
- Newcastle University Medicine Malaysia, Iskandar Puteri 79200, Johor, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
| | - Chun-Wai Mai
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
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Recent Trends in Nanomedicine-Based Strategies to Overcome Multidrug Resistance in Tumors. Cancers (Basel) 2022; 14:cancers14174123. [PMID: 36077660 PMCID: PMC9454760 DOI: 10.3390/cancers14174123] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 08/23/2022] [Accepted: 08/23/2022] [Indexed: 11/16/2022] Open
Abstract
Cancer is the leading cause of economic and health burden worldwide. The commonly used approaches for the treatment of cancer are chemotherapy, radiotherapy, and surgery. Chemotherapy frequently results in undesirable side effects, and cancer cells may develop resistance. Combating drug resistance is a challenging task in cancer treatment. Drug resistance may be intrinsic or acquired and can be due to genetic factors, growth factors, the increased efflux of drugs, DNA repair, and the metabolism of xenobiotics. The strategies used to combat drug resistance include the nanomedicine-based targeted delivery of drugs and genes using different nanocarriers such as gold nanoparticles, peptide-modified nanoparticles, as well as biomimetic and responsive nanoparticles that help to deliver payload at targeted tumor sites and overcome resistance. Gene therapy in combination with chemotherapy aids in this respect. siRNA and miRNA alone or in combination with chemotherapy improve therapeutic response in tumor cells. Some natural substances, such as curcumin, quercetin, tocotrienol, parthenolide, naringin, and cyclosporin-A are also helpful in combating the drug resistance of cancer cells. This manuscript summarizes the mechanism of drug resistance and nanoparticle-based strategies used to combat it.
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Ranasinghe R, Mathai M, Zulli A. Revisiting the therapeutic potential of tocotrienol. Biofactors 2022; 48:813-856. [PMID: 35719120 PMCID: PMC9544065 DOI: 10.1002/biof.1873] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Accepted: 05/13/2022] [Indexed: 12/14/2022]
Abstract
The therapeutic potential of the tocotrienol group stems from its nutraceutical properties as a dietary supplement. It is largely considered to be safe when consumed at low doses for attenuating pathophysiology as shown by animal models, in vitro assays, and ongoing human trials. Medical researchers and the allied sciences have experimented with tocotrienols for many decades, but its therapeutic potential was limited to adjuvant or concurrent treatment regimens. Recent studies have focused on targeted drug delivery by enhancing the bioavailability through carriers, self-sustained emulsions, nanoparticles, and ethosomes. Epigenetic modulation and computer remodeling are other means that will help increase chemosensitivity. This review will focus on the systemic intracellular anti-cancer, antioxidant, and anti-inflammatory mechanisms that are stimulated and/or regulated by tocotrienols while highlighting its potent therapeutic properties in a diverse group of clinical diseases.
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Affiliation(s)
- Ranmali Ranasinghe
- Institute of Health and Sport, College of Health and MedicineVictoria UniversityMelbourneVictoriaAustralia
| | - Michael Mathai
- Institute of Health and Sport, College of Health and MedicineVictoria UniversityMelbourneVictoriaAustralia
| | - Anthony Zulli
- Institute of Health and Sport, College of Health and MedicineVictoria UniversityMelbourneVictoriaAustralia
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Sim W, Lim WM, Hii LW, Leong CO, Mai CW. Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases. World J Gastroenterol 2022; 28:1934-1945. [PMID: 35664961 PMCID: PMC9150054 DOI: 10.3748/wjg.v28.i18.1934] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Revised: 03/17/2022] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor development. Regardless, it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses, thus allowing continuous tumor growth and development. Immune evasion has emerged as a significant factor contributing to the progression and immune resistance of pancreatic cancer. Compared with other cancers, pancreatic cancer has a tumor microenvironment that can resist most treatment modalities, including emerging immunotherapy. Sadly, the use of immunotherapy has yet to bring significant clinical breakthrough among pancreatic cancer patients, suggesting that pancreatic cancer has successfully evaded immunomodulation. In this review, we summarize the impact of genetic alteration and epigenetic modification (especially histone deacetylases, HDAC) on immune evasion in pancreatic cancer. HDAC overexpression significantly suppresses tumor suppressor genes, contributing to tumor growth and progression. We review the evidence on HDAC inhibitors in tumor eradication, improving T cells activation, restoring tumor immunogenicity, and modulating programmed death 1 interaction. We provide our perspective in targeting HDAC as a strategy to reverse immune evasion in pancreatic cancer.
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Affiliation(s)
- Wynne Sim
- School of Medicine, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Wei-Meng Lim
- School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
- Center for Cancer and Stem Cell Research, Institute for Research, Development, and Innovation, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Ling-Wei Hii
- School of Pharmacy, International Medical University, Kuala Lumpur 57000, Malaysia
- Center for Cancer and Stem Cell Research, Institute for Research, Development, and Innovation, International Medical University, Kuala Lumpur 57000, Malaysia
| | - Chee-Onn Leong
- Center for Cancer and Stem Cell Research, Institute for Research, Development, and Innovation, International Medical University, Kuala Lumpur 57000, Malaysia
- AGTC Genomics, Kuala Lumpur 57000, Malaysia
| | - Chun-Wai Mai
- State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
- Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
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De Silva L, Fu JY, Htar TT, Wan Kamal WHB, Kasbollah A, Muniyandy S, Chuah LH. Biodistribution Study of Niosomes in Tumor-Implanted BALB/C Mice Using Scintigraphic Imaging. Front Pharmacol 2022; 12:778396. [PMID: 35069200 PMCID: PMC8777053 DOI: 10.3389/fphar.2021.778396] [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: 09/16/2021] [Accepted: 12/10/2021] [Indexed: 11/13/2022] Open
Abstract
The purpose of this work was to study the biodistribution of niosomes in tumor-implanted BALB/c mice using gamma scintigraphy. Niosomes were first formulated and characterized, then radiolabeled with Technetium-99 m (99mTc). The biodistribution of 99mTc-labeled niosomes was evaluated in tumor-bearing mice through intravenous injection and imaged with gamma scintigraphy. The labeled complexes possessed high radiolabeling efficiency (98.08%) and were stable in vitro (>80% after 8 h). Scintigraphic imaging showed negligible accumulation in the stomach and thyroid, indicating minimal leaching of the radiolabel in vivo. Radioactivity was found mainly in the liver, spleen and kidneys. Tumor-to-muscle ratio indicated a higher specificity of the formulation for the tumor area. Overall, the formulated niosomes are stable both in vitro and in vivo, and show preferential tumor accumulation.
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Affiliation(s)
- Leanne De Silva
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
| | - Ju-Yen Fu
- Nutrition Unit, Malaysian Palm Oil Board, Bandar Baru Bangi, Malaysia
| | - Thet Thet Htar
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
| | | | - Azahari Kasbollah
- Medical Technology Division, Malaysian Nuclear Agency, Bangi, Malaysia
| | - Saravanan Muniyandy
- Department of Pharmacy, Fatima College of Health Sciences, Al Ain, United Arab Emirates
| | - Lay-Hong Chuah
- School of Pharmacy, Monash University Malaysia, Bandar Sunway, Malaysia
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11
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Functionalized niosomes as a smart delivery device in cancer and fungal infection. Eur J Pharm Sci 2021; 168:106052. [PMID: 34740786 DOI: 10.1016/j.ejps.2021.106052] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 10/13/2021] [Accepted: 10/25/2021] [Indexed: 12/17/2022]
Abstract
Various diseases remain untreated due to lack of suitable therapeutic moiety or a suitable drug delivery device, especially where toxicities and side effects are the primary reason for concern. Cancer and fungal infections are diseases where treatment schedules are not completed due to severe side effects or lengthy treatment protocols. Advanced treatment approaches such as active targeting and inhibition of angiogenesis may be preferred method for the treatment for malignancy over the conventional method. Niosomes may be a better alternative drug delivery carrier for various therapeutic moieties (either hydrophilic or hydrophobic) and also due to ease of surface modification, non-immunogenicity and economical. Active targeting approach may be done by targeting the receptors through coupling of suitable ligand on niosomal surface. Moreover, various receptors (CD44, folate, epidermal growth factor receptor (EGFR) & Vascular growth factor receptor (VGFR)) expressed by malignant cells have also been reviewed. The preparation of suitable niosomal formulation also requires considerable attention, and its formulation depends upon various factors such as selection of non-ionic surfactant, method of fabrication, and fabrication parameters. A combination therapy (dual drug and immunotherapy) has been proposed for the treatment of fungal infection with special consideration for surface modification with suitable ligand on niosomal surface to sensitize the receptors (C-type lectin receptors, Toll-like receptors & Nucleotide-binding oligomerization domain-like receptors) present on immune cells involved in fungal immunity. Certain gene silencing concept has also been discussed as an advanced alternative treatment for cancer by silencing the mRNA at molecular level using short interfering RNA (si-RNA).
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