標題: Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules
作者: Ho, Shu-Yi
Chen, Pin-Rong
Chen, Chia-Hung
Tsai, Nu-Man
Lin, Yu-Hsin
Lin, Chen-Si
Chuang, Cheng-Hsun
Huang, Xiao-Fan
Chan, Yi-Lin
Liu, Yen-Ku
Chung, Chen-Han
Weng, Shun-Long
Liao, Kuang-Wen
交大名義發表
生物科技學系
分子醫學與生物工程研究所
National Chiao Tung University
Department of Biological Science and Technology
Institute of Molecular Medicine and Bioengineering
關鍵字: LPPC;Gene therapy;Anti-angiogenesis;RBDV;VEGFR
公開日期: 9-Apr-2020
摘要: Background The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. Results LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. Conclusions The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.
URI: http://dx.doi.org/10.1186/s12951-020-00610-9
http://hdl.handle.net/11536/154407
DOI: 10.1186/s12951-020-00610-9
期刊: JOURNAL OF NANOBIOTECHNOLOGY
Volume: 18
Issue: 1
起始頁: 0
結束頁: 0
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