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论文类型： 期刊论文

发表时间： 2018-12-07

发表刊物： JOURNAL OF MATERIALS CHEMISTRY B

收录刊物： SCIE

卷号： 6

期号： 45

页面范围： 7530-7542

ISSN号： 2050-750X

摘要： 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.