载吲哚菁绿和多柔比星自组装胶束的构建及体外抗肿瘤及其转移的评价

发布时间：2018-07-14 10:27

【摘要】：本研究通过p H敏感的腙键共价连接疏水性化疗药物多柔比星(doxorubicin,DOX)和亲水性抗肿瘤转移的低分子量肝素(low molecular weight heparin,LH)合成了低分子量肝素-多柔比星胶束(LH-DOX),并物理包载光热剂吲哚菁绿(indocyanine green,ICG),以透析法制备了具有p H敏感的载吲哚菁绿的低分子量肝素-多柔比星聚合物胶束(LH-DOX/ICG)。该胶束粒径为(148.7±2.1)nm,在电镜下呈形态规则的球形,粒径均一,并具有良好的稳定性和生物相容性。体外释放结果显示,DOX的释放具有p H敏感性,ICG有一定的缓释效果。ICG包载于胶束后与游离ICG具有相似的光热效应。一方面,划痕愈合实验显示,在激光照射下LH-DOX/ICG胶束具有良好的抗肿瘤转移能力;另一方面,细胞凋亡及细胞毒性实验表明,在激光照射下该胶束诱导黑色素瘤B16F10细胞凋亡的能力和对细胞毒性作用明显增加。因此,LH-DOX/ICG胶束具有良好的前景,用于光疗-化疗联合治疗黑色素瘤。
[Abstract]:In this study, low molecular weight heparin micelle (LH-DOX) was synthesized by covalently linking doxorubicinine doxorubicin (doxorubicindox) and low molecular weight heparin LH (LH-DOX). A low molecular weight heparin-doxorubicin polymer micelle (LH-DOX / ICG) with p-H sensitive indocyanine green (indocyanine greenine green) was prepared by dialysis. The particle size of the micelle was (148.7 卤2.1nm). The micelle was spherical in shape and uniform in size under electron microscope, and had good stability and biocompatibility. The results of in vitro release showed that the release of DOX was of pH sensitivity and ICG had a certain slow-release effect. ICG encapsulated in micelles had a similar photothermal effect to that of free ICG. On the one hand, scratch healing experiments showed that LH-DOX / ICG micelles had good anti-metastasis ability under laser irradiation, on the other hand, apoptosis and cytotoxicity tests showed that, The ability and cytotoxicity of the micelle to induce apoptosis of melanoma B16F10 cells were significantly increased under laser irradiation. Therefore, LH-DOX / ICG micelles have good prospects for phototherapy combined with chemotherapy in the treatment of melanoma.
【作者单位】：四川大学华西药学院靶向药物与传递系统教育部重点实验室;
【基金】：国家自然科学基金资助项目(81773658)
【分类号】：R943;R96

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