Poly(l-glutamic acid)-Based Zwitterionic Polymer in a Charge Conversional Shielding System for Gene Therapy of Malignant Tumors.,ACS Applied Materials & Interfaces

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Poly(l-glutamic acid)-Based Zwitterionic Polymer in a Charge Conversional Shielding System for Gene Therapy of Malignant Tumors.
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2020-04-14 , DOI: 10.1021/acsami.0c02769
Jie Chen _{1,

2,

3} , Zhaopei Guo _{1,

3} , Zixue Jiao ₁ , Lin Lin _{1,

2,

3} , Caina Xu _{1,

3} , Huayu Tian _{1,

2,

3} , Xuesi Chen _{1,

2,

3}

Affiliation

Recently, pH-sensitive polymers have received extensive attention in tumor therapy. However, the rapid response to pH changes is the key to achieving efficient treatment. Here, a novel shielding system with a rapidly pH-responsive polymer (PAMT) is synthesized by click reaction between poly(γ-allyl-l-glutamate) and thioglycolic acid or 2-(Boc-amino)ethanethiol. The zwitterionic biodegradable polymer PAMT, which is negatively charged at physiological pH, can be used to shield positively charged nanoparticles. PAMT is electrostatically attached to the surface of the positively charged PEI/pDNA complex to form a ternary complex. The zwitterionic PAMT-shielded complex exhibits rapid charge conversion when the pH decreases from 7.4 to 6.8. For the in vivo tumor inhibition experiment, PAMT/PEI/shVEGF injected intravenously shows a more significant inhibitory effect on tumor growth. The excellent results are mainly attributed to introduction of the zwitterionic copolymer PAMT, which can shield the positively charged PEI/shVEGF complex in physiological conditions, while the surface potential of the shielded complexes changes to a positive charge in the acidic tumor environment.

中文翻译：

电荷转化屏蔽系统中基于聚（1-谷氨酸）的两性离子聚合物，用于恶性肿瘤的基因治疗。

近来，pH敏感性聚合物在肿瘤治疗中受到广泛关注。但是，对pH变化的快速响应是实现有效处理的关键。在此，通过聚（γ-烯丙基-1-谷氨酸）与巯基乙酸或2-（Boc-氨基）乙硫醇之间的点击反应，合成了具有快速pH响应聚合物（PAMT）的新型屏蔽系统。两性离子生物可降解聚合物PAMT在生理pH下带负电，可用于屏蔽带正电的纳米粒子。PAMT静电连接到带正电的PEI / pDNA复合物的表面，形成三元复合物。当pH从7.4降低到6.8时，两性离子PAMT保护的复合物表现出快速的电荷转化。对于体内肿瘤抑制实验，静脉注射PAMT / PEI / shVEGF对肿瘤生长显示出更显着的抑制作用。优异的结果主要归功于两性离子共聚物PAMT的引入，该共聚物可在生理条件下屏蔽带正电的PEI / shVEGF复合物，而屏蔽的复合物的表面电势在酸性肿瘤环境中变为正电荷。

更新日期：2020-04-23

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