Premium
Poly(ornithine‐co‐arginine‐co‐glycine‐co‐aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor‐Penetrating Agent
Author(s) -
Yu Haiyang,
Tang Zhaohui,
Zhang Dawei,
Song Wantong,
Duan Taicheng,
Gu Jingkai,
Chen Xuesi
Publication year - 2015
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201500040
Subject(s) - chemistry , polymerization , polymer chemistry , arginine , aspartic acid , ornithine , cytotoxicity , nuclear chemistry , stereochemistry , amino acid , biophysics , biochemistry , organic chemistry , in vitro , polymer , biology
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 of N ‐δ‐carbobenzoxy‐l‐ornithine N ‐carboxyanhydride [Orn(Cbz)‐NCA)], l‐glycine N ‐carboxyanhydride (Gly‐NCA) and β‐benzyl l‐aspartate N ‐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 site in vivo skin 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.