Systemic and tumor-targeted delivery of siRNA by cyclic NGR and isoDGR motif-containing peptides

Biomaterials Science
Yuanyu HuangZicai Liang

Abstract

The drug development of siRNA has been seriously hindered by the lack of an effective, safe and clinically applicable delivery system. The cyclic NGR motif and its isomerization product isoDGR recruit CD13 and integrin as their specific receptors, both of which are overexpressed by tumor and neovascular cells. In this study, a bi-functional peptide, named NGR-10R, was designed and tested for siRNA delivery in vitro and in vivo. Through the formation of peptide/siRNA nanoparticles, RNase resistance was greatly enhanced for the siRNAs. Both FACS and confocal assays revealed that the peptide/siRNA complexes were effectively internalized by MDA-MB-231 cells. Gene silencing assays indicated that anti-Lamin A/C siRNA delivered by NGR-10R robustly repressed gene expression in MDA-MB-231 and HUVEC (a CD13(+)/αvβ3(+) cell). Importantly, the siRNAs were efficiently delivered into tumor tissues and localized around the nuclei, as revealed by in vivo imaging and cryosection examination. In summary, NGR-10R not only efficiently delivered siRNAs into MDA-MB-231 cells in vitro but also delivered siRNAs into tumor cells in vivo, taking advantage of its specific binding to CD13 (neovascular) or αvβ3 (MDA-MB-231). Therefore, the NGR-10R peptide ...Continue Reading

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Citations

Sep 13, 2016·ACS Applied Materials & Interfaces·Yuhuan LiLesheng Teng
Jun 3, 2017·PloS One·Kata Nóra EnyediGábor Mező
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Jun 26, 2020·ACS Applied Materials & Interfaces·Mengjie ZhangYuanyu Huang

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