Highly Efficient and Safe Delivery of VEGF siRNA by Bioreducible Fluorinated Peptide Dendrimers for Cancer Therapy.

Abstract	RNA interference (RNAi) has a great promise in treating various acquired and hereditary diseases. However, it remains highly desirable to develop new delivery system to circumvent complex extra- and intracellular barriers for successful clinical translation. Here, we report on a versatile polymeric vector, bioreducible fluorinated peptide dendrimers (BFPD), for efficient and safe small interfering RNA (siRNA) delivery. In virtue of skillfully integrating all of the unique advantages of reversible cross-linking, fluorination, and peptide dendrimers, this novel vector can surmount almost all extra- and intracellular barriers associated with local siRNA delivery through highly improved physiological stability and serum resistance, significantly increased intratumoral enrichment, cellular internalization, successful facilitation of endosomal escape, and cytosolic siRNA release. BFPD polyplexes, carrying small interfering vascular endothelial growth factor (siVEGF), demonstrated excellent VEGF silencing efficacy (∼65%) and a strong capability for inhibiting HeLa cell proliferation. More importantly, these polyplexes showed superior performance in long-term enrichment in the tumor sites and had a high level of tumor growth inhibition. Furthermore, these polyplexes not only exhibited excellent in vivo antitumor efficacy but also demonstrated superior biocompatibility, compared with LPF2000, both in vivo and in vitro. These findings indicate that BFPD is an efficient and safe siRNA delivery system and has remarkable potential for RNAi-based cancer treatment.
Authors	Xiaojun Cai, Haofang Zhu, Yanmei Zhang, Zhongwei Gu
Journal	ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 9 Issue 11 Pg. 9402-9415 (Mar 22 2017) ISSN: 1944-8252 [Electronic] United States
PMID	28228013 (Publication Type: Journal Article)
Chemical References	Dendrimers Peptides RNA, Small Interfering Vascular Endothelial Growth Factor A
Topics	Dendrimers (chemistry) HeLa Cells Humans Peptides RNA, Small Interfering Vascular Endothelial Growth Factor A

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