Combination therapy of pDNA and siRNA by versatile carriers composed of poly(l-serine) modified polyethylenimines

Abstract

Multi-gene-based approaches for tumor therapy have yet to be developed. Accordingly, we explored a combination treatment strategy by loading two kinds of therapeutic reagents simultaneously: pDNA and siRNA. Polyethylenimine–poly(L-serine) (PEI–PSer) obtained via ring-opening polymerization of L-serine N-carboxyanhydride initiated by polyethylenimines served as a potent cationic gene carrier. Proton nuclear magnetic resonance spectroscopy and gel permeation chromatography confirmed the successful preparation of PEI–PSer copolymers. The morphologies and effective binding capacities of PEI–PSer and genes were evaluated through gel retardation, scanning electron microscopy, and particle size and zeta potential assays. PEI–PSer displayed pDNA transfection and siRNA knockdown efficacy without affecting cell viability. The high gene transfer efficacy was mainly due to the excellent intracellular trafficking ability of PEI–PSer, as confirmed by confocal laser scanning microscopy and flow cytometry. Cell apoptosis assay further confirmed the combination antitumor effect aroused by the co-delivery of pKH-rev-casp-3 and siBcl2 by PEI–PSer. This study introduced a new carrier that delivers pDNA and siRNA simultaneously, thereby providing a potential strategy for tumor treatment.