Oligopeptide-terminated poly(β-amino ester)s for highly efficient gene delivery and intracellular localization
Oligopeptide-terminated poly(β-amino ester)s for highly efficient gene delivery and intracellular localization
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DOI：
10.1016/j.actbio.2013.12.054
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发表时间：
2014-05-01
影响因子：
9.7
通讯作者：
Borros, Salvador
中科院分区：
文献类型：
--
作者：
Segovia, Nathaly;Dosta, Pere;Borros, Salvador
临床应用基因治疗的主要限制是缺乏稳健、安全和有效的基因传递载体。本文介绍了基于末端寡肽的聚-氨基酯（pBAE）的基因传递新聚合。作者开发了寡肽修饰的pBAE- pdna纳米颗粒，与其他末端修饰的pBAE和商业转染剂相比，具有更好的细胞活力和更高的转染效率。基因在高容性细胞系中的表达非常高，但在低容性细胞系中的转染效率高度依赖于寡肽组成和纳米颗粒配方。此外，在pBAE配方中使用选定的寡肽导致颗粒在细胞内的优先定位。对高效pBAE配方进行颗粒分析，发现其颗粒大小和电荷特征不同，表明颗粒表面具有化学伪类型，与寡肽的化学性质有关。总之，在pBAE末端用富含胺的寡肽进行化学修饰是开发未来基因治疗应用的递送系统的有力策略。(C) 2014材料学报Elsevier Ltd.出版。版权所有。
The main limitation of gene therapy towards clinics is the lack of robust, safe and efficient gene delivery vectors. This paper describes new polycations for gene delivery based on poly(beta-amino ester)s (pBAE) containing terminal oligopeptides. The authors developed oligopeptide-modified pBAE-pDNA nanopartides that achieve better cellular viability and higher transfection efficacy than other end-modified pBAE and commercial transfection agents. Gene expression in highly permissive cell lines was remarkably high, but transfection efficiency in less-permissive cell lines was highly dependent on oligopeptide composition and nanoparticle formulation. Moreover, the use of selected oligopeptides in the pBAE formulation led to preferential intracellular localization of the particles. Particle analysis of highly efficient pBAE formulations revealed different particle sizes and charge features, which indicates chemical pseudotyping of the particle surface, related to the oligopeptide chemical nature. In conclusion, chemical modification at the termini of pBAE with amine-rich oligopeptides is a powerful strategy for developing delivery systems for future gene therapy applications. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.