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.

研究以可降解树枝状介孔二氧化硅（DMSNs）为载体负载农药氯虫苯甲酰胺（CHL），然后进行聚乙烯亚胺（PEI）功能化修饰并在其表面进一步负载农药多杀菌素（SPI），制备得到了双响应型双项负载纳米农药制剂（DMSNs-CHL-PEI-SPI）。DMSNs-CHL-PEI-SPI具有良好的分散性、叶面粘附性和生物安全性，实现了一个纳米材料对两种农药（CHL和SPI）的双项负载，载药量高达52.03 %。此外，DMSNs-CHL-PEI-SPI具有良好的双信号控制释放行为，可实现同时在两种环境刺激（GSH、pH）作用下对农药的控制释放，在碱性以及GSH共同存在的情况下，CHL和SPI均达到最大释放。叶片浸渍法和温室实验发现，相比相同浓度的单项负载纳米农药制剂(DMSNs-CHL、DMSNs-PEI-SPI)和物理混配制剂(CHL/SPI、DMSNs-CHL/DMSNs-PEI-SPI)，DMSNs-CHL-PEI-SPI不仅提高了对害虫（草地贪夜蛾）的杀虫毒力，而且显著延长了农药的杀虫持效期，是一种协同两类杀虫剂活性的高效农药控释剂，对提高纳米农药的应用价值具有重要意义。