Incorporation of a therapeutic antibody into nanosized drug delivery systems can improve their target specificity. This work reports an antibody-conjugated targeted delivery system composed of polymer-dendron conjugates. Trastuzumab is chosen as the targeting moiety, since it is clinically used against tumor cells expressing HER2 receptors. A micellar delivery system was generated using amphiphilic polymer-dendron conjugates containing a fourth-generation polyester dendron as the hydrophobic block and a linear poly(ethylene glycol) (PEG) chain as the hydrophilic block. After preparation of docetaxel loaded (ca. 10% wt) micelles, trastuzumab was conjugated onto the micellar shell using an amidation reaction. Micelles remained stable after conjugation of the antibody, with a slight increase in size from 179 nm to 185 nm upon functionalization. Docetaxel release was determined to be responsive to acidic pH, and over the course of 30 h, 54% drug release was measured in acidic media, whereas it was around 30% under neutral conditions. Cytotoxicity experiments on MCF-7 and SK-OV-3 cell lines displayed improved toxicity levels for targeted micelles in comparison with the non-targeted counterparts, whereas pulse-chase experiments indicated effectiveness of micellar formulations and the presence of targeting groups. Cellular internalization experiments using fluorescence microscopy and flow cytometry further demonstrated the enhanced cellular uptake of antibody conjugated targeted micelles.

中文翻译：

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曲妥珠单抗使用树枝状聚合物共轭物靶向多西他赛的胶束递送。

将治疗性抗体掺入纳米级药物递送系统中可以改善其靶标特异性。这项工作报告了由聚合物-树枝状共轭物组成的抗体共轭靶向递送系统。选择曲妥珠单抗作为靶向部分，因为它在临床上用于表达HER2受体的肿瘤细胞。使用包含第四代聚酯树枝状结构作为疏水性嵌段和线性聚（乙二醇）（PEG）链作为亲水性嵌段的两亲性聚合物-树枝状共轭物生成胶束递送系统。在制备负载多西他赛的胶束（约10％wt）后，使用酰胺化反应将曲妥珠单抗缀合到胶束壳上。胶束结合后，胶束保持稳定，功能化后尺寸从179 nm略微增加到185 nm。已确定多西紫杉醇的释放对酸性pH有反应，并且在30小时的过程中，在酸性介质中测得54％的药物释放，而在中性条件下约为30％。在MCF-7和SK-OV-3细胞系上的细胞毒性实验显示，与未靶向的对应物相比，靶向胶束的毒性水平有所提高，而脉冲追踪实验则表明胶束制剂的有效性和靶向组的存在。使用荧光显微镜和流式细胞仪进行的细胞内化实验进一步证明了抗体结合的靶向胶束的细胞摄取增加。在MCF-7和SK-OV-3细胞系上的细胞毒性实验显示，与未靶向的对应物相比，靶向胶束的毒性水平有所提高，而脉冲追踪实验则表明胶束制剂的有效性和靶向组的存在。使用荧光显微镜和流式细胞仪进行的细胞内化实验进一步证明了抗体结合的靶向胶束的细胞摄取增加。在MCF-7和SK-OV-3细胞系上的细胞毒性实验显示，与未靶向的对应物相比，靶向胶束的毒性水平有所提高，而脉冲追踪实验则表明胶束制剂的有效性和靶向组的存在。使用荧光显微镜和流式细胞仪进行的细胞内化实验进一步证明了抗体结合的靶向胶束的细胞摄取增加。