还原敏感性材料是通过在高分子材料的主链、侧链或者交联结构中引入二硫键合成得到的。由于细胞内外谷胱甘肽等还原性物质的浓度相差较大，形成了巨大的还原势能梯度，还原敏感性材料作为药物输送的载体，能够在循环系统和细胞外液中保持稳定，而进入细胞后在高浓度的还原性物质作用下迅速降解、释放药物，从而显著提高核酸药物转染效率，降低高分子材料的毒性，有望作为理想的核酸药物载体。还原敏感性材料合成方法主要有两种，一是选择含有二硫键的反应物直接参与聚合物的合成或修饰反应，二是在聚合物中引入巯基，通过氧化反应，使巯基转变为二硫键。本文主要介绍近年来还原敏感性材料应用于核酸药物输送的研究进展，并根据引入二硫键方法的不同分类讨论材料的合理设计与合成。%Reducible polymers are characterized by introduction of disulfide bonds in their structures. Such polymers re- main highly stable in circulation and extracellular environment, but quickly go through degradation and release cargo in the cytosol because of the natural existence of the redox potential gradients between extracellular and intracellular space. This remarkable features render them increased transfection rate and decreased cytotoxicity. Reduction-sensitive polymers show great prospect for construction of ideal nucleic acid delivery system. There are two major approaches used to incorporate re- ducible bonds in polymers, first synthesizing cationic polymers with reactants which contain disulfide linkages, second in- troducing thiols into the structures that can convert to disulfide bonds through oxidation. This review discusses recent ad- vances in application of bioreducible polymers for nucleic acid delivery, with particular focus on rational design and syn- thesis of these polymers.
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