Key Laboratory Of Polymer Ecomaterialschangchun Institute Of Applied Chemistrychinese Academy Of Scienceschangchun130022P R China

Laboratory of, China

Key Laboratory Of Polymer Ecomaterialschangchun Institute Of Applied Chemistrychinese Academy Of Scienceschangchun130022P R China

Laboratory of, China
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Yu H.,Key Laboratory Of Polymer Ecomaterialschangchun Institute Of Applied Chemistrychinese Academy Of Scienceschangchun130022P R China | Tang Z.,Key Laboratory Of Polymer Ecomaterialschangchun Institute Of Applied Chemistrychinese Academy Of Scienceschangchun130022P R China | Zhang D.,Key Laboratory Of Polymer Ecomaterialschangchun Institute Of Applied Chemistrychinese Academy Of Scienceschangchun130022P R China | Song W.,Key Laboratory Of Polymer Ecomaterialschangchun Institute Of Applied Chemistrychinese Academy Of Scienceschangchun130022P R China | And 3 more authors.
Macromolecular Bioscience | Year: 2015

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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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