题目：

Cationic Polypeptoids with Optimized Molecular Characteristics toward Efficient Non-Viral Gene Delivery

作者：

Lipeng Zhu^1,§, Jessica M. Simpson^2,§, Xin Xu¹, Hua He¹, Donghui Zhang^2,* and Lichen Yin^1,*

单位：

¹Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou 215123, P.R. China.

²Department of Chemistry and Macromolecular Studies Group, Louisiana State University, Baton Rouge, LA 70803, USA.

摘要：

The rational design of gene vectors relies on the understanding of their structure-property relationship. Polypeptoids, structural isomers of natural polypeptides, hold great potentials as gene delivery vectors due to their facial preparation, structural tunability, and most importantly, desired proteolytic stability. We herein designed a library of polypeptoids with different cationic side-chain terminal groups, degrees of polymerization (DP), side-chain lengths, and incorporated aliphatic side chains, attempting to unravel the structure-property relationship toward maximized gene delivery efficiency while minimized cytotoxicity. In HeLa cells, polypeptoid bearing primary amine side-chain terminal group exhibited remarkably higher transfection efficiency than its analogues containing secondary, tertiary, or quaternary amine groups. Elongation of the polypeptoid backbone length (from 28 to251 mer) led to enhanced DNA condensation level as well as cellular uptake level, while at the meantime caused higher cytotoxicity. Upon a proper balance between DNA uptake and cytotoxicity, polypeptoid with DP of 46 afforded the highest transfection efficiency. Elongating the aliphatic spacer between backbone and side amine groups enhanced the hydrophobicity of side chains, which resulted in notably increased membrane activities and transfection efficiency. Further incorporation of hydrophobic decyl side chains led to an improvement of transfection efficiency by ~6fold. The top-performing material identified, P11, mediated successful gene transfection under serum-containing conditions, outperforming commercial transfection reagent PEI by nearly 4 orders of magnitude. In consistence with its serum-resistant properties, P11 further enabled effective transfection in vivo following intratumoral injection to melanoma-bearing mice. This study will help the rational design of polypeptoid-based gene delivery materials, and the best-performing material identified may provide a potential supplement to existing gene vectors.

影响因子：

7.504

分区情况：

一区

链接：

http://pubs.acs.org/doi/10.1021/acsami.7b06031