Meng Fenghua, Hennink Wim E, Zhong Zhiyuan
Biomedical Polymers Laboratory and Jiangsu Key Laboratory of Organic Chemistry, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Ren-Ai Road 199, Suzhou 215123, PR China.
Biomaterials. 2009 Apr;30(12):2180-98. doi: 10.1016/j.biomaterials.2009.01.026. Epub 2009 Feb 5.
Reduction-sensitive biodegradable polymers and conjugates have emerged as a fascinating class of biomedical materials that can be elegantly applied for intracellular triggered gene and drug delivery. The design rationale of reduction-sensitive polymers and conjugates usually involves incorporation of disulfide linkage(s) in the main chain, at the side chain, or in the cross-linker. Reduction-sensitive polymers and conjugates are characterized by an excellent stability in the circulation and in extracellular fluids, whereas they are prone to rapid degradation under a reductive environment present in intracellular compartments such as the cytoplasm and the cell nucleus. This remarkable feature renders them distinct from their hydrolytically degradable counterparts and extremely intriguing for the controlled cytoplasmic delivery of a variety of bioactive molecules including DNA, siRNA, antisense oligonucleotide (asODN), proteins, drugs, etc. This review presents recent advances in the development of reduction-sensitive biodegradable polymers and conjugates, with particular focus on the up-to-date design and chemistry of various reduction-sensitive delivery systems including liposomes, polymersomes, polymeric micelles, DNA containing nanoparticles, polyion complex micelles, nano- and micro-gels, nanotubes, and multi-layered thin films. It is evident that reduction-sensitive biodegradable polymers and conjugates are highly promising functional biomaterials that have enormous potential in formulating sophisticated drug and gene delivery systems.
对还原敏感的可生物降解聚合物及共轭物已成为一类引人入胜的生物医学材料，可巧妙地应用于细胞内触发的基因和药物递送。对还原敏感的聚合物及共轭物的设计原理通常涉及在主链、侧链或交联剂中引入二硫键。对还原敏感的聚合物及共轭物的特点是在循环系统和细胞外液中具有出色的稳定性，而在细胞内区室（如细胞质和细胞核）存在的还原环境下易于快速降解。这一显著特性使其有别于可水解降解的同类材料，对于包括DNA、小干扰RNA、反义寡核苷酸（asODN）、蛋白质、药物等多种生物活性分子的可控细胞质递送极具吸引力。本综述介绍了对还原敏感的可生物降解聚合物及共轭物开发方面的最新进展，特别关注各种对还原敏感的递送系统（包括脂质体、聚合物囊泡、聚合物胶束、含DNA纳米颗粒、聚离子复合物胶束、纳米和微凝胶、纳米管以及多层薄膜）的最新设计和化学原理。显然，对还原敏感的可生物降解聚合物及共轭物是极有前景的功能性生物材料，在构建精密的药物和基因递送系统方面具有巨大潜力。
