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

机译:酶法合成含硒两亲脂族聚碳酸酯作为氧化反应性药物传递载体

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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 -CMP _(45) ). 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 -CMP _(45) efficiently encapsulated doxorubicin (DOX) via self-assembly in aqueous solution and showed an excellent ability to regulate the release of DOX in response to H _(2) O _(2) 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 -CMP _(45) . These collective data suggested the potential use of mPEG- b -CMP _(45) as a biocompatible and smart drug delivery vehicle.
机译:尽管功能性脂族聚碳酸酯(APC)作为刺激响应性生物材料已引起了广泛的研究兴趣,但大多数功能性APC是由有害的有机金属催化剂或有机催化剂制成的。在本文中,开发了一种基于酶促聚合的简便合成策略来构建含硒两亲脂族聚碳酸酯(mPEG-b -CMP_(45))。具体而言,硒在其骨架结构中暴露于异常的ROS水平后会经历疏水-亲水转变,从而为ROS触发的药物释放提供了有希望的平台。该两亲性mPEG- b -CMP _(45)通过在水溶液中自组装有效地封装了阿霉素(DOX),并且在生物学上表现出出色的调节H_(2)O _(2)的能力来调节DOX的释放。相关浓度(100μM)。这些装载有DOX的纳米粒子可以很容易地内化到U87细胞中,并具有DOX固有的抗肿瘤特性,而在正常细胞HL​​-7702中却表现出低得多的细胞毒性。而且,在许多情况下,硒的引入引起了该材料的高细胞毒性,但是HL-7702细胞的细胞毒性结果证明了mPEG-b-CMP_(45)具有良好的生物相容性。这些收集的数据表明,mPEG-b -CMP_(45)作为生物相容性和智能药物递送载体的潜在用途。

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