PEG修饰在基因递送系统中的应用:优势、不足及改善策略

Application of PEGylation in gene delivery systems:advantages,limitations and strategy

基因治疗是治疗多种疾病的一种强有力的手段。有效递送目的基因至病灶治疗部位是基因治疗成功的关键。目前常用的基因载体大多为阳离子纳米微粒,会引起细胞毒性和体内免疫反应,其表面通常需要PEG修饰来掩蔽部分正电荷,以降低血液循环途径中与内源性阴离子物质的非特异性结合,延长载药粒子的血液循环时间和降低毒性。然而,PEG修饰也会带来一系列的问题,如降低基因递送载体的细胞摄取、阻碍基因药物"内吞体逃逸"而降低转染效率,以及重复注射PEG化载体引起的"加速血液清除"(accelerated blood clearance,ABC)现象等。本文综述了PEG修饰应用在基因递送系统中的优势和不足,并对PEG修饰改善策略和寻找有潜力的PEG替代物进行了探讨。

Gene therapy is a new potent biomedical technology for treating various diseases. Developing a targeted gene delivery system is the crucial scientific problem for successful gene therapy. Cationic nanocarriers are usually used for gene delivery,but they may cause in vivo toxicity and immune response. In order to acquire long circulation in blood as well as reduce in vivo toxicity of the cationic nanocarriers,PEGylation is the most wide strategy,which can shield surface positive charges and reduce the non-specific interaction between endogenous protein and nanocarrier during circulation based on the presence of PEG on the surface of nanocarrier. Unfortunately,lower cellular uptake,lower transfection efficacy caused by inefficient ＂endosomal escape＂and accelerated blood clearance（ ABC） phenomenon after repeated administration are found in PEGylation nanocarriers. This review will summarize the advantages and limitations of PEGylation in gene delivery system,and discuss the possible improvement strategies or potential PEG alternatives to overcome these limitations.