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首页> 外文期刊>RSC Advances >Synthesis and self-assembly behavior of pH-responsive star-shaped POSS-(PCL-P(DMAEMA-co-PEGMA))16 inorganic/organic hybrid block copolymer for the controlled intracellular delivery of doxorubicin
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Synthesis and self-assembly behavior of pH-responsive star-shaped POSS-(PCL-P(DMAEMA-co-PEGMA))16 inorganic/organic hybrid block copolymer for the controlled intracellular delivery of doxorubicin

机译：pH-响应星形POSS-（PCL-P（DMAEMA-CO-PEGMA））16无机/有机杂化嵌段共聚物的合成和自组装行为用于受控的多柔比星的细胞内递送

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In this work, well-defined amphiphilic polyhedral oligomeric silsesquioxane (POSS) star-shaped inorganic/organic hybrid block copolymers with poly(ε-caprolactone)-poly(2-(dimethylamino)ethyl methacrylate)- co -poly(ethylene glycol) methacrylate (POSS-PCL-P(DMAEMA- co -PEGMA)) _(16) were synthesized with different PCL segments via thiol-ene click reaction, ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP), which were confirmed by Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance ( ~(1) H NMR), gel permeation chromatography (GPC), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). Subsequently, the polymers could self-assemble into micelles in aqueous solution, which were investigated by dynamic light scattering (DLS), ultraviolet-visible spectroscopy (UV-vis) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these triblock copolymers in water was investigated at different pH values of 5.0 and 7.4 for controlled doxorubicin release; the results indicated that the release rate of DOX could be effectively controlled by altering the pH and the release of drug loading efficiency (DLE) was up to 82% (w/w). Furthermore, CCK-8 assays and confocal laser scanning microscopy (CLSM) against HeLa cells indicated that the micelles had no associated cytotoxicity, possessed good biodegradability and biocompatibility, and identified the location of the DOX in HeLa cells. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action, and minimize the side effects of free DOX. Moreover, these flexible micelles with on-off switched drug release may offer a promising method to deliver a wide variety of hydrophobic payloads to tumor cells for cancer therapy.
机译：在这项工作中，定义的两亲多型多面体低聚硅氧烷（POSS）星形无机/有机杂化嵌段共聚物与聚（ε-己内酯） - 聚（2-（二甲基氨基）甲基丙烯酸乙酯） - CO -poly（乙二醇）甲基丙烯酸酯（POLL-PCL-P（DMAEMA-CO -PEGMA））_（16）通过硫醇-NE键点击反应，环开口聚合（ROP）和原子转移自由基聚合（ATRP）合成。通过傅里叶变换红外光谱（FT-IR），质子核磁共振（〜（1）H NMR），凝胶渗透色谱（GPC），X射线光电子能谱（XPS）和热重分析（TGA）。随后，聚合物可以通过动态光散射（DLS），紫外 - 可见光谱（UV-VIS）和透射电子显微镜（TEM）来自组装成水溶液中的胶束。在5.0和7.4的不同pH值下研究这些三嵌段共聚物在水中的pH响应性自组装行为，用于控制的多柔比星释放。结果表明，通过改变pH可以有效地控制DOX的释放速率，并释放药物负载效率（DLE）高达82％（w / w）。此外，CCK-8测定和抗HeLa细胞的共聚焦激光扫描显微镜（CLSM）表明胶束没有相关的细胞毒性，具有良好的生物降解性和生物相容性，并鉴定了在HeLa细胞中DOX的位置。 DOX加载的胶束可以容易地进入细胞并产生所需的药理学作用，并最大限度地减少自由DOX的副作用。此外，这些具有开关式药物释放的柔性胶束可以提供有希望的方法，以为肿瘤细胞提供各种疏水有效载荷，用于癌症治疗。

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