Poly(ornithine-co-arginine-co-glycine-co-aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor-Penetrating Agent
Poly(ornithine-co-arginine-co-glycine-co-aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor-Penetrating Agent
复制标题
聚（鸟氨酸-共-精氨酸-共-甘氨酸-共-天冬氨酸）：通过NCA聚合制备及其作为聚合物肿瘤渗透剂的潜力
DOI：
10.1002/mabi.201500040
复制
发表时间：
2015
影响因子：
4.6
通讯作者：
Chen Xuesi
中科院分区：
文献类型：
--
作者：
Yu Haiyang;Tang Zhaohui;Zhang Dawei;Song Wantong;Duan Taicheng;Gu Jingkai;Chen Xuesi
A novel random copolypeptide of ornithine, arginine, glycine, and aspartic acid [Poly(ornithine‐co‐arginine‐co‐glycine‐co‐aspartic acid), Poly(O,R,G,D)] has been prepared through ring‐opening polymerization ofN‐δ‐carbobenzoxy‐l‐ornithineN‐carboxyanhydride [Orn(Cbz)‐NCA)], l‐glycineN‐carboxyanhydride (Gly‐NCA) and β‐benzyl l‐aspartateN‐carboxyanhydride [Asp(Bn)‐NCA], following by subsequent deprotection and guanidization. The structure of Poly(O,R,G,D) was confirmed by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Low cytotoxicity of Poly(O,R,G,D) was confirmed from MTT assay. The Poly(O,R,G,D) contain some internal sequences of RXXR (X= O, R, G, or D) that could be proteolytically cleaved to expose the cryptic CendR element and bind to Neuropilin‐1. This would lead to vascular and tissue permeabilization. Therefore trypsin‐cleaved Poly(O,R,G,D) increase the vascular leakage of Evans blue from dermal microvessels at the injection sitein vivoskin permeability assay. The intratumoral injection of the Poly(O,R,G,D) significantly enhanced the concentration of cisplatin‐loaded nanoparticles in MCF‐7 solid tumors. These results show that Poly(O,R,G,D) could increase the vascular leakage and tissue penetration of nanoparticles in a solid tumor and can be used as a potential polymeric tumor‐penetrating agent.
