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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

機(jī)譯：基于多功能兩親星型共聚物的pH /還原雙刺激響應(yīng)交聯(lián)膠束：合成和可控的抗癌藥物釋放

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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.
機(jī)譯：已經(jīng)構(gòu)建了用于制備兩親性星形共聚物pH /還原刺激反應(yīng)性交聯(lián)膠束（SCM）的新方法，該方法是用于良好控制的抗腫瘤藥物阿霉素（DOX）釋放的智能藥物遞送系統(tǒng)。 SCM的CMC值較低，為5.3 mg / L。空白和裝有DOX的SCM均呈球形，尺寸約為100-180 nm。此外，還通過動(dòng)態(tài)光散射（DLS）來確定SCM的良好穩(wěn)定性和良好的pH /還原敏感性。 SCM在血液和正常組織中具有較低的DOX釋放，而在腫瘤中較高的谷胱甘肽（GSH）濃度和/或較低的pH值條件下具有快速釋放的DOX，這證明了它們的pH /還原雙重反應(yīng)性。此外，我們進(jìn)行了熱力學(xué)分析，以研究DOX和聚合物膠束在DOX釋放過程中的相互作用。在pH 7.4和pH 5.0條件下的熱力學(xué)參數(shù)值表明，DOX的釋放是吸熱的，并且主要受靜電相互作用力的控制。在pH 5.0和10 mM GSH條件下，靜電相互作用，化學(xué)鍵和疏水相互作用共同促進(jìn)了DOX的釋放。由于空白SCM的細(xì)胞毒性較低，而DOX加載的SCM的細(xì)胞毒性良好，結(jié)果表明SCM可以形成智能的癌癥微環(huán)境響應(yīng)藥物遞送系統(tǒng)。釋放動(dòng)力學(xué)和熱力學(xué)分析為藥物分子與聚合物基質(zhì)之間的相互作用提供了理論基礎(chǔ)，這有助于為針對(duì)癌癥治療的抗癌藥物釋放的定向設(shè)計(jì)和控制提供路線圖。

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