br Acknowledgements br This work
This work was supported by the Natural Science Foundation of Shandong Province (ZR2016HB05 and ZR2016HB45), the open project of Shandong Collaborative Innovation Center for Antibody Drugs (CIC-AD1827), the Postdoctoral Science Foundation of China (2018M632607), and the National Natural Science Foundation of China (81600087).
XJL and WHM: Data curation, Methodology and Writing - original draft; SZN and LW: Data curation and Validation; JD and LLZ: Data curation, Formal analysis and Writing - review & editing SDR and XJL: Funding acquisition, Conceptualization and Writing - review & editing.
Conflicts of interest
Authors declare no competing financial interests.
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Contents lists available at ScienceDirect
International Journal of Pharmaceutics
journal homepage: www.elsevier.com/locate/ijpharm
Cell cytotoxicity, immunostimulatory and antitumor eﬀects of lipid content T of liposomal delivery platforms in cancer immunotherapies. A comprehensive in-vivo and in-vitro study
Amin Reza Nikpoora, Mahmoud Reza Jaafarib,c, Parvin Zamanid,e, Manouchehr Teymourif, Hamed Gouklanig, Ehsan Saburih, Shahrzad Amiri Darbanc,e, Ali Badieee,c, Ali Bahramifari, Mahdi Fasihi-Ramandij, Ramezan Ali Taherik,
a Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
b Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
c Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
d Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
e Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
f Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran
g Infectious and Tropical Diseases Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
h Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
i Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
j Molecular Biology Research Center, System Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
k Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Cellular immune response
Liposome is one of the promising technologies for antigen delivery in cancer immunotherapies. It seems that the phospholipid content of liposomes can act as immunostimulatory molecules in cancer immunotherapy. In the present study, the immunological properties of diﬀerent phospholipid content of liposomal antigen delivery platforms were investigated. To this aim, F1 to F4 naïve liposomes (without tumor-specific loaded antigens) of positively charged DOTAP/Cholesterol/DOPE (4/4/4 mol ratio), negatively charged DMPC/DMPG/Cholesterol/ DOPE (15/2/3/5), negatively charged DSPC/DSPG/Cholesterol/DOPE (15/2/3/5) and PEGylated HSPC/ mPEG2000-DSPE/Cholesterol (13/110) liposomal compositions were administered in mice bearing C26 colon carcinoma to assess tumor therapy. Moreover, In-vitro studies were conducted, including cytotoxicity assay, serum cytokines measurements, IFN-γ and IL-4 ELISpot assay, T cells subpopulation frequencies assay. The liposomes containing DOTAP and DOPE (F1 liposomes) were able to stimulate cytotoxic T lymphocytes signals such as IFN-γ secretions. In parallel, the aforementioned phospholipids stimulated secretion of IL-4 and IL-17 cytokines from T helper cells. However, these liposomes did not improve survival indices in mice. As conclusion, DOTAP and DOPE contained liposomes (F1 liposomes) stimulate a mixture of Th1 and Th2 immune responses in a tumor-specific antigens-free manner in mice bearing C26 colon carcinoma. Therefore, phospholipid compo-sition of liposomes merits consideration in designing antigen-containing liposomes for cancer immunotherapy.