Nam, H. Ku, S.H. Yoon, H.Y. Kim, K. Kwon, I.C. Kim, S.H. Lee, J.B. 2024-01-19T20:02:11Z 2024-01-19T20:02:11Z 2021-08-31 2019-06 2366-3987 https://pubs.kist.re.kr/handle/201004/119967 Despite the superb therapeutic potential of siRNA technology, its clinical application are still limited due to the inherent instability and lack of systemic delivery issues. Recently, the development of long-chain siRNA has been proposed as a strategy to improve in vivo stability, particularly for efficient physical integration of siRNA molecules into gene carriers. Herein, concatemeric siRNAs are enzymatically synthesized through a rolling circle transcription process, and form stable RNA interference (RNAi) nanocomplexes with a redox-sensitive glycol chitosan derivative to systemically deliver the concatemeric siRNAs to tumor tissues. The enzymatically generated RNAi nanocomplexes (RNCs) have higher particle stability and less cytotoxicity than the conventional polyelectrolyte complexes. The therapeutic potential of the RNC formulation is verified in vivo as well as in vitro using VEGF as an antiangiogenic target for RNAi-based anticancer therapy. After systemic administration, RNC is specifically accumulated in tumor tissues and shows a high inhibitory effect on tumor growth. According to the results, the RNC can be considered as a platform technology for efficient tumor-targeted siRNA delivery systems. ？ 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim English Blackwell Publishing Ltd Enhancing Systemic Delivery of Enzymatically Generated RNAi Nanocomplexes for Cancer Therapy Article 10.1002/adtp.201900014 1 Advanced Therapeutics, v.2, no.6 Advanced Therapeutics 2 6 N scopus 000506357900006 2-s2.0-85086312942 Pharmacology & Pharmacy Pharmacology & Pharmacy Article chitosan derivative circular DNA polyelectrolyte small interfering RNA vasculotropin animal experiment animal model antineoplastic activity apoptosis Article cancer inhibition cancer therapy cell viability controlled study cross linking cytotoxicity disulfide bond down regulation drug delivery system endocytosis enzymatic degradation flow cytometry fluorescence imaging gel electrophoresis gene silencing human human cell intracellular transport macropinocytosis male molecular weight mouse nonhuman particle size physical chemistry priority journal promoter region prostate cancer RNA interference RNAi therapeutics scanning electron microscopy static electricity surface charge SVEC4-10 cell line tumor volume concatemeric siRNA rolling circle transcription structural modification systemic siRNA delivery system tumor-targeted delivery