Abstract

A highly efficient siRNA vector (Zn-PQD) capable of selectively silencing genes in cancer cells was obtained by using ROS-cleavable DED to crosslink low molecular weight (LMW) polyethylene imine (PEI) modified by self-fluorescent metal coordinatied multifunctional module Zn-QS. Under the combined action of DED cross-linking and Zn-QS modification, Zn-PQD performs well in the siRNA delivery process in cancer cells, including siRNA condensation, cell uptake, endosome escape, and siRNA release. Zn-PQD exhibited higher transfection efficiency than commercial PEI25k and Lipo2k in multiple cancer cell lines including HepG2, HeLa, 4 T1, H520 and PANC-1, as well as cancer treatment-related stem cell rADSC. Ultimately, Zn-PQD can achieve extremely high and selective gene silencing effects in cancer cells (with a gene silencing rate of 98.3% in HepG2). This work is expected to provide an efficient and safe siRNA carrier for the future tumor siRNA therapy and its study of fluorescence mediated mechanism.

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