Fluorinated Acid‐Labile Branched Hydroxyl‐Rich Nanosystems for Flexible and Robust Delivery of Plasmids,Small

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Fluorinated Acid‐Labile Branched Hydroxyl‐Rich Nanosystems for Flexible and Robust Delivery of Plasmids
Small ( IF 13.0 ) Pub Date : 2018-09-20 , DOI: 10.1002/smll.201803061
Yu Qi ₁ , Haiqing Song ₁ , Haihua Xiao ₂ , Gang Cheng ₃ , Bingran Yu ₁ , Fu-Jian Xu ₁

Affiliation

Nucleic acid‐based therapy specially needs a safe and robust delivery vector. Herein, a novel fluorinated acid‐labile branched hydroxyl‐rich polycation (ARP‐F) is proposed for the flexible and effective delivery nanovector of different plasmids including reporter genes and the Cas9 plasmid. Acid‐responsive polycation (ARP) with plentiful ortho ester linkages and hydroxyl groups is first synthesized via a facile one‐pot ring‐opening polymerization, followed by decoration of fluorinated alkyl chains onto ARP to achieve ARP‐F. ARP‐F possesses good pH‐responsive degradability, biocompatibility, and its preliminary transfection ability evaluated by reporter plasmids pRL‐CMV (encoding Renilla luciferase) and pEGFP‐N1 (encoding enhanced green fluorescent protein) is also excellent. CRISPR‐Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR‐associated nuclease 9) technology is a potent genome‐editing tool. The subsequent delivery of pCas9‐surv (one typical all‐in‐one Cas9 plasmid) mediated by ARP‐F exhibits impressive in vitro and in vivo tumor inhibition performances. In addition, the combination of ARP‐F/pCas9‐surv with temozolomide could further enhance tumor inhibition activities by increasing the sensitivity of cancer cells to anticancer drugs. Such high‐performance polycation would provide a very promising means to produce efficient delivery nanovectors of versatile plasmids.

中文翻译：

含氟酸不稳定支链富含羟基的纳米系统，可灵活，稳健地传递质粒

基于核酸的疗法特别需要安全可靠的递送载体。本文提出了一种新颖的氟化酸不稳定支链羟基富集聚阳离子（ARP-F），用于灵活而有效地递送不同质粒的纳米载体，包括报告基因和Cas9质粒。首先通过简单的一锅开环聚合反应合成具有丰富的原酸酯键和羟基的酸响应性聚阳离子（ARP），然后将氟化烷基链装饰到ARP上以实现ARP-F。ARP-F具有良好的pH响应降解性，生物相容性，并且通过报道质粒pRL-CMV（编码海藻荧光素酶）和pEGFP-N1（编码增强的绿色荧光蛋白）评估的初步转染能力也非常出色。CRISPR‐Cas9（聚类的规则间隔的短回文重复序列/ CRISPR关联的核酸酶9）技术是一种有效的基因组编辑工具。由ARP-F介导的pCas9-surv（一种典型的多合一Cas9质粒）的后续递送表现出令人印象深刻的体外和体内肿瘤抑制性能。此外，ARP-F / pCas9-surv与替莫唑胺的组合可通过增加癌细胞对抗癌药物的敏感性来进一步增强肿瘤抑制活性。这种高性能的聚阳离子将为生产高效的多功能质粒纳米载体提供非常有希望的手段。由ARP-F介导的pCas9-surv（一种典型的多合一Cas9质粒）的后续递送表现出令人印象深刻的体外和体内肿瘤抑制性能。此外，ARP-F / pCas9-surv与替莫唑胺的组合可通过增加癌细胞对抗癌药物的敏感性来进一步增强肿瘤抑制活性。这种高性能的聚阳离子将为生产高效的多功能质粒纳米载体提供非常有希望的手段。由ARP-F介导的pCas9-surv（一种典型的多合一Cas9质粒）的后续递送表现出令人印象深刻的体外和体内肿瘤抑制性能。此外，ARP-F / pCas9-surv与替莫唑胺的组合可通过增加癌细胞对抗癌药物的敏感性来进一步增强肿瘤抑制活性。这种高性能的聚阳离子将为生产高效的多功能质粒纳米载体提供非常有希望的手段。

更新日期：2018-09-20

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