Center for Bionanoengineering and Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Zheda Road 38, 310027 Hangzhou, China.
Changchun Institute of Applied Chemistry, Key Lab of Polymer Ecomaterials, Changchun, China.
Adv Drug Deliv Rev. 2017 Jun 1;115:115-154. doi: 10.1016/j.addr.2017.07.021. Epub 2017 Aug 1.
Gene therapy represents a promising cancer treatment featuring high efficacy and limited side effects, but it is stymied by a lack of safe and efficient gene-delivery vectors. Cationic polymers and lipid-based nonviral gene vectors have many advantages and have been extensively explored for cancer gene delivery, but their low gene-expression efficiencies relative to viral vectors limit their clinical translations. Great efforts have thus been devoted to developing new carrier materials and fabricating functional vectors aimed at improving gene expression, but the overall efficiencies are still more or less at the same level. This review analyzes the cancer gene-delivery cascade and the barriers, the needed nanoproperties and the current strategies for overcoming these barriers, and outlines PEGylation, surface-charge, size, and stability dilemmas in vector nanoproperties to efficiently accomplish the cancer gene-delivery cascade. Stability, surface, and size transitions (3S Transitions) are proposed to resolve those dilemmas and strategies to realize these transitions are comprehensively summarized. The review concludes with a discussion of the future research directions to design high-performance nonviral gene vectors.
基因治疗是一种很有前途的癌症治疗方法，具有高效和低副作用的特点，但由于缺乏安全有效的基因传递载体而受到限制。阳离子聚合物和基于脂质的非病毒基因载体具有许多优点，已被广泛探索用于癌症基因传递，但与病毒载体相比，其基因表达效率较低，限制了其临床转化。因此，人们致力于开发新的载体材料和构建功能性载体，以提高基因表达，但整体效率或多或少仍处于同一水平。本文分析了癌症基因传递级联和障碍、所需的纳米特性以及克服这些障碍的当前策略，并概述了载体纳米特性中的聚乙二醇化、表面电荷、大小和稳定性难题，以有效地完成癌症基因传递级联。稳定性、表面和大小转变（3S 转变）被提出以解决这些难题，并全面总结了实现这些转变的策略。本文最后讨论了设计高性能非病毒基因载体的未来研究方向。
