101. Preparation of PEGylated cationic nanoliposome-siRNA complexes for cancer therapy
- Author
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Fateme Haghiralsadat, Ghasem Amoabediny, Tymour Forouzanfar, Behrouz Zandieh-Doulabi, Marco N. Helder, Samira Naderinezhad, Oral and Maxillofacial Surgery / Oral Pathology, CCA - Cancer biology and immunology, Amsterdam Movement Sciences - Restoration and Development, Maxillofacial Surgery (VUmc), and MKA Vumc (OII, ACTA)
- Subjects
Cell Survival ,Biomedical Engineering ,Cancer therapy ,Pharmaceutical Science ,Medicine (miscellaneous) ,02 engineering and technology ,Gene delivery ,Transfection ,Polyethylene Glycols ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,In vivo ,Cell Line, Tumor ,Zeta potential ,Humans ,Cationic liposome ,Gene Silencing ,RNA, Small Interfering ,Adaptor Proteins, Signal Transducing ,Liposome ,Chemistry ,Cationic polymerization ,General Medicine ,021001 nanoscience & nanotechnology ,Nanostructures ,Gene Expression Regulation, Neoplastic ,030220 oncology & carcinogenesis ,Liposomes ,Biophysics ,PEGylation ,0210 nano-technology ,Biotechnology - Abstract
Cationic liposomes have been investigated as non-viral vectors for gene delivery for more than a decade to overcome challenges associated with viral gene delivery. However, due to instability of liposomes, siRNA delivery is still a serious problem. In this study, we developed stealth PEGylated liposome formulations and focused on the effects of PEGylated liposomes on parameters related to size, zeta potential, polydispersity index, siRNA-loading efficiency and long-term stability of the siRNA-liposome complex. We were able to generate siRNA lipoplexes that could be very efficiently loaded, did not aggregate, could be stored at 4 °C for at least 6 months with only marginal release (1–5%) of siRNA and enhanced intracellular delivery of siRNA. Moreover, we could demonstrate that PEGylation positively contributed to all these parameters compared to liposomes, which were not PEGylated. The prepared lipoplex was successfully silenced J1P1 expression in MG-63 osteosarcoma cell line. In conclusion, our novel PEGylated liposomes have high potential for systemic delivery of siRNA and can improve in vivo stability of free siRNA and also siRNA lipoplexes.
- Published
- 2018
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