Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery.

摘要: Long circulation, cell internalization, endosomal escape and small interfering RNA (siRNA) release to the cytoplasm are prerequisite considerations for siRNA delivery vectors. Herein, a kind of sheddable nanoparticles (NPs) with micelle architecture were fabricated by using an intracellular-activated polycation-detachable copolymer (PECssD), which was prepared introducing highly reducing environment-responsive disulfide linkages between PEGylated polycaprolactone (PCL) grafted polycation, poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). The PECssD self-assembled NPs includes biodegradable hydrophobic PCL core, PEG shield detachable comb-like polycation surface. stable nanosized complexes siRNA, termed PECssD/siRNA micelleplexes, formed, could prolong improve accumulation retention in tumor tissue, be favorable internalization. In particular, cleavage intracellular microenvironment subsequent dissociation PDMAEMA/siRNA polyplexes from cores micelleplexes also confirmed, facilitated efficient siRNA. As result, distribution enhanced subsequently promoted efficiency gene silencing. Furthermore, systemic administration carrying siPlk1 (polo-like kinase 1 specific siRNA) induced tumor-suppressing effect HeLa-Luc xenograft murine model. Therefore, devised strategy address requirements multistep process core is expected entrap antitumor drugs or other therapeutic agents combined therapies.