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Enzymatic synthesis of selenium-containing amphiphilic aliphatic polycarbonate as an oxidation-responsive drug delivery vehicle

Author:
Yang, Xian-Ling, Xing, Xiu, Li, Jun, Liu, Yan-Hong, Wang, Na, Yu, Xiao-Qi
Source:
RSC advances 2019 v.9 no.11 pp. 6003-6010
ISSN:
2046-2069
Subject:
antineoplastic activity, aqueous solutions, biocompatibility, biocompatible materials, cytotoxicity, doxorubicin, drug carriers, hydrogen peroxide, nanoparticles, neoplasms, organocatalysts, polymerization, selenium
Abstract:
Although functional aliphatic polycarbonates (APCs) have attracted prominent research interest as stimuli-responsive biomaterials, the majority of functional APCs are fabricated by detrimental organometallic catalysts or organo-catalysts. Herein, a facile synthetic strategy based on enzymatic polymerization was developed to construct a selenium-containing amphiphilic aliphatic polycarbonate (mPEG-b-CMP₄₅). Specifically, the selenium in its backbone framework underwent a hydrophobic–hydrophilic transition upon exposure to the abnormal ROS level of the tumor, thus providing a promising platform for ROS-triggered drug release. This amphiphilic mPEG-b-CMP₄₅ efficiently encapsulated doxorubicin (DOX) via self-assembly in aqueous solution and showed an excellent ability to regulate the release of DOX in response to H₂O₂ at biologically relevant concentrations (100 μM). These DOX-loaded nanoparticles could easily be internalized into U87 cells and possess the inherent antitumor properties of DOX, while they exhibited much lower cytotoxicity in normal cells HL-7702. Moreover, in many cases, the introduction of selenium caused high cytotoxicity of the materials, but the cytotoxicity results in HL-7702 cells demonstrated the good biocompatibility of mPEG-b-CMP₄₅. These collective data suggested the potential use of mPEG-b-CMP₄₅ as a biocompatible and smart drug delivery vehicle.
Agid:
6314299