Armin Mahmoud Salehi Kheshti1, Farnaz Hajizadeh2, Asal Barshidi1, Bentolhoda Rashidi1, Farbod Ebrahimi3, Simin Bahmanpour1, Vahid Karpisheh1, Fatemeh Karimian Noukabadi4, Fariba Karoon Kiani1, Hadi Hassannia5, Fatemeh Atyabi6, Seyed Hossein Kiaie1,7, Fatah Kashanchi8, Jamshid Gholizadeh Navashenaq9, Hamed Mohammadi10, Rafieh Bagherifar7, Reza Jafari11,12, Naime Majidi Zolbanin13,14,15, Farhad Jadidi-Niaragh16,17,18. 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Nanoparticle Process Technology, Faculty of Engineering, University of Duisburg-Essen, Duisburg, Germany. 4. Department of Biotechnology, Falavarjan Branch, Islamic Azad University, Isfahan, Iran. 5. Immunogenetic Research Center, Faculty of Medicine and Amol Faculty of Paramedical Sciences, Mazandaran University of Medical Sciences, Sari, Iran. 6. Nanotechnology Research Centre, Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. 7. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, 6715847141, Iran. 8. Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Manassas, Virginia, USA. 9. Noncommunicable Diseases Research Center, Bam University of Medical Sciences, Bam, Iran. 10. Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. 11. Nephrology and Kidney Transplant Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran. 12. Hematology, Immune Cell Therapy, and Stem Cell Transplantation Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran. 13. Hematology, Immune Cell Therapy, and Stem Cell Transplantation Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran. majidiz.n@umsu.ac.ir. 14. Experimental and Applied Pharmaceutical Research Center, Urmia University of Medical Sciences, Urmia, Iran. majidiz.n@umsu.ac.ir. 15. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran. majidiz.n@umsu.ac.ir. 16. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. jadidif@tbzmed.ac.ir. 17. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. jadidif@tbzmed.ac.ir. 18. Research Center for Integrative Medicine in Aging, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. jadidif@tbzmed.ac.ir.
Abstract
PURPOSE: The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine. METHODS: For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells. RESULTS: The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models. CONCLUSIONS: These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.
PURPOSE: The invention and application of new immunotherapeutic methods can compensate for the inefficiency of conventional cancer treatment approaches, partly due to the inhibitory microenvironment of the tumor. In this study, we tried to inhibit the growth of cancer cells and induce anti-tumor immune responses by silencing the expression of the β-catenin in the tumor microenvironment and transmitting interleukin (IL)-15 cytokine to provide optimal conditions for the dendritic cell (DC) vaccine. METHODS: For this purpose, we used folic acid (FA)-conjugated SPION-carboxymethyl dextran (CMD) chitosan (C) nanoparticles (NPs) to deliver anti-β-catenin siRNA and IL-15 to cancer cells. RESULTS: The results showed that the codelivery of β-catenin siRNA and IL-15 significantly reduced the growth of cancer cells and increased the immune response. The treatment also considerably stimulated the performance of the DC vaccine in triggering anti-tumor immunity, which inhibited tumor development and increased survival in mice in two different cancer models. CONCLUSIONS: These findings suggest that the use of new nanocarriers such as SPION-C-CMD-FA could be an effective way to use as a novel combination therapy consisting of β-catenin siRNA, IL-15, and DC vaccine to treat cancer.
Authors: Udit N Verma; Rama M Surabhi; Aurelia Schmaltieg; Carlos Becerra; Richard B Gaynor Journal: Clin Cancer Res Date: 2003-04 Impact factor: 12.531
Authors: Shanthi Ganesh; Xue Shui; Kevin P Craig; Jihye Park; Weimin Wang; Bob D Brown; Marc T Abrams Journal: Mol Ther Date: 2018-09-13 Impact factor: 11.454
Authors: Ming Yang; Olamide Tosin Olaoba; Chunye Zhang; Eric T Kimchi; Kevin F Staveley-O'Carroll; Guangfu Li Journal: Pharmaceutics Date: 2022-08-04 Impact factor: 6.525