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首页> 美国卫生研究院文献>Polymers >pH/Reduction Dual-Stimuli-Responsive Cross-Linked Micelles Based on Multi-Functional Amphiphilic Star Copolymer: Synthesis and Controlled Anti-Cancer Drug Release
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pH/Reduction Dual-Stimuli-Responsive Cross-Linked Micelles Based on Multi-Functional Amphiphilic Star Copolymer: Synthesis and Controlled Anti-Cancer Drug Release

机译：基于多功能两亲星型共聚物的pH /还原双刺激响应交联胶束：合成和可控的抗癌药物释放

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Novel approach has been constructed for preparing the amphiphilic star copolymer pH/reduction stimuli-responsive cross-linked micelles (SCMs) as a smart drug delivery system for the well-controlled anti-tumor drug doxorubicin (DOX) release. The SCMs had a low CMC value of 5.3 mg/L. The blank and DOX-loaded SCMs both had a spherical shape with sizes around 100–180 nm. In addition, the good stability and well pH/reduction-sensitivity of the SCMs were determined by dynamic light scattering (DLS) as well. The SCMs owned a low release of DOX in bloodstream and normal tissues while it had a fast release in tumor higher glutathione (GSH) concentration and/or lower pH value conditions, which demonstrates their pH/reduction dual-responsiveness. Furthermore, we conducted the thermodynamic analysis to study the interactions between the DOX and polymer micelles in the DOX release process. The values of the thermodynamic parameters at pH 7.4 and at pH 5.0 conditions indicated that the DOX release was endothermic and controlled mainly by the forces of an electrostatic interaction. At pH 5.0 with 10 mM GSH condition, electrostatic interaction, chemical bond, and hydrophobic interactions contributed together on DOX release. With the low cytotoxicity of blank SCMs and well cytotoxicity of DOX-loaded SCMs, the results indicated that the SCMs could form a smart cancer microenvironment-responsive drug delivery system. The release kinetic and thermodynamic analysis offer a theoretical foundation for the interaction between drug molecules and polymer matrices, which helps provide a roadmap for the oriented design and control of anti-cancer drug release for cancer therapy.
机译：已经构建了用于制备两亲性星形共聚物pH /还原刺激反应性交联胶束（SCM）的新方法，该方法是用于良好控制的抗肿瘤药物阿霉素（DOX）释放的智能药物递送系统。 SCM的CMC值较低，为5.3 mg / L。空白和装有DOX的SCM均呈球形，尺寸约为100-180 nm。此外，还通过动态光散射（DLS）来确定SCM的良好稳定性和良好的pH /还原敏感性。 SCM在血液和正常组织中具有较低的DOX释放，而在肿瘤中较高的谷胱甘肽（GSH）浓度和/或较低的pH值条件下具有快速释放的DOX，这证明了它们的pH /还原双重反应性。此外，我们进行了热力学分析，以研究DOX和聚合物胶束在DOX释放过程中的相互作用。在pH 7.4和pH 5.0条件下的热力学参数值表明，DOX的释放是吸热的，并且主要受静电相互作用力的控制。在pH 5.0和10 mM GSH条件下，静电相互作用，化学键和疏水相互作用共同促进了DOX的释放。由于空白SCM的细胞毒性较低，而DOX加载的SCM的细胞毒性良好，结果表明SCM可以形成智能的癌症微环境响应药物递送系统。释放动力学和热力学分析为药物分子与聚合物基质之间的相互作用提供了理论基础，这有助于为针对癌症治疗的抗癌药物释放的定向设计和控制提供路线图。

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