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Indexed by:期刊论文

Date of Publication:2018-12-07

Journal:JOURNAL OF MATERIALS CHEMISTRY B

Included Journals:SCIE

Volume:6

Issue:45

Page Number:7530-7542

ISSN No.:2050-750X

Abstract:Stimuli-responsive delivery systems show great promise in meeting the requirements of several delivery stages to achieve satisfactory gene transfection. This report describes a novel stimuli-responsive nanocarrier consisting of a dual stimuli-responsive chitosan (SCS) core and a polyethyleneimine (PEI) and polyethylene glycol (PEG) corona. The SCS core was constructed by cross-linking bio-safe chitosan saccharide via pH-sensitive hydrazone bonds and redox-sensitive disulfide bonds, which conferred the nanocarrier with a dual stimuli-responsive property. PEG and low-molecular-weight PEI were further immobilized on the core to endow the synthesized SCS-g-PEI-g-PEG with improved gene condensation, prolonged circulation and enhanced lysosome escape. In vitro and in vivo Birc5-shRNA delivery results revealed that significantly enhanced gene expression and tumor inhibition were achieved by SCS-g-PEI-g-PEG, compared with the non-stimuli-responsive counterpart CS-g-PEI-g-PEG. Moreover, the SCS-g-PEI-g-PEG nanocarrier was biocompatible as shown in both in vitro and in vivo toxicity evaluations. This study may provide a promising strategy for constructing an efficient and bio-safe delivery system for gene therapy.