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.
Highlights
In the eld of biomaterials, tremendous efforts have been devoted for the development of stimuli-responsive drug delivery systems that deliver therapeutic agents in a controlled manner
The detailed assignments of protons for other copolymers were shown in Fig. S2.† And the degree of polymerization (DP) of selenium-containing units in the copolymers were calculated by comparing the integral ratio of the peaks at 3.38 ppm with 2.04 ppm (SeCH2CH2)
The Mw values of the copolymers kept increasing on the addition of HSPMC monomers, which was in good agreement with hypothesis
Summary
In the eld of biomaterials, tremendous efforts have been devoted for the development of stimuli-responsive drug delivery systems that deliver therapeutic agents in a controlled manner. Cellular uptake and intracellular drug release study of DOX-loaded micelles was visualized by confocal laser scanning microscopy (CLSM, LSM 780). Scheme 1 The synthesis of mPEG-b-CMP45 block copolymers and preparation of DOX-loaded mPEG-b-CMP45 micelles as oxidationresponsive drug delivery vehicle.
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