载紫杉醇的PEG修饰的大黄酸偶联物胶束的细胞摄取及活体成像研究

目的 探究载紫杉醇(paclitaxel,PTX)的聚乙二醇(polyethyleneglycol,PEG)修饰的大黄酸偶联物胶束的细胞摄取及活体成像情况。方法 将环境响应型荧光探针P4/P2与药物PTX共载于mPEG-羧甲基壳聚糖-大黄酸(CRmP)偶联物胶束中，制备(P4+PTX)/CRmP胶束。以MCF-7细胞为细胞模型，利用激光共聚焦显微镜和流式细胞仪分析该胶束被MCF-7细胞摄取的情况；以H22皮下移植瘤小鼠为模型，在体和离体成像分析该胶束在体内的分布情况。结果 (P4+PTX)/CRmP胶束以完整的胶束形式被MCF-7细胞内吞摄入，分布于细胞质。(P2+PTX)/CRmP胶束在荷瘤小鼠的肝脏和肿瘤部位较多聚集，并于实验时间内在肿瘤部位不断累积。结论 该胶束以完整的胶束形式被肿瘤细胞摄取，在体内有一定的肝靶向性和肿瘤靶向性。

Study on Cellular Uptake and in Vivo Imaging of Paclitaxel-loaded PEG-modified Rhein Conjugate Micelles

OBJECTIVE To investigate the cellular uptake and in vivo imaging of paclitaxel(PTX)-loaded polyethylene glycol(PEG)-modified rhein conjugate micelles. METHODS (P4/P2+PTX)/CRmP micelles were prepared by co-loading environment-responsive fluorescent probes P4/P2 and PTX into CRmP micelles. Using MCF-7 cells as cell models, the uptake of the micelles by MCF-7 cells was analyzed by laser confocal microscopy and flow cytometry. The H22 subcutaneous transplanted tumor mice were used as animal models, and the distribution of the micelles in vivo and in vitro were analyzed by in vivo imaging system. RESULTS (P4+PTX)/CRmP micelles in the intact form were internalized by MCF-7 cells and distributed in the cytoplasm. (P2+PTX)/CRmP micelles were more accumulated in the liver and tumor sites in vivo, and gradually accumulated at the tumor sites during the experimental time. CONCLUSION The intact micelles can be taken up by tumor cells, and have liver and tumor targeting properties in vivo.