Co-assembly of doxorubicin and curcumin targeted micelles for synergistic delivery and improving anti-tumor efficacy
Co-assembly of doxorubicin and curcumin targeted micelles for synergistic delivery and improving anti-tumor efficacy
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共组装阿霉素和姜黄素靶向胶束以协同递送并提高抗肿瘤功效
DOI：
10.1016/j.ejpb.2016.11.033
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发表时间：
2017-03-01
影响因子：
4.9
通讯作者：
Tu, Pengfei
中科院分区：
文献类型：
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作者：
Ma, Wenzhuan;Guo, Qiang;Tu, Pengfei
化疗药物在抗肿瘤治疗中存在一系列局限性，主要表现为多药耐药和严重的不良反应。两种或两种以上协同治疗药物的共给药系统是解决这些局限性的有效策略。本研究采用透明质酸-维生素E琥珀酸酯（HA-VES）接枝共聚物（HA-VES）为载体，制备了具有肿瘤靶向活性的阿霉素（DOX）和姜黄素（Cur）两种增效药物的共递送胶束（DOX + Cur）-PMs，并将其同时递送到肿瘤细胞中，以提高阿霉素的治疗效果。(DOX+ Cur）-PMs具有粒径均匀、包封率高、缓释性好、胶体稳定性好等特点。体外细胞毒性实验表明，（DOX + Cur）-PMs对DOX耐药的MCF-7/Adr细胞具有最强的细胞毒性和最高的细胞凋亡诱导活性。此外，（DOX + Cur）-PMs通过能量依赖性和小窝介导的内吞作用更有效地内化到癌细胞中并增强细胞对DOX的摄取，并通过CD 44靶向递送和释放的Cur的协同作用显著逆转MDR效应。更重要的是，体内实验结果表明，（DOX + Cur）-PMs不仅表现出更好的肿瘤蓄积和肿瘤靶向性，更有效地抑制4 T1荷瘤小鼠的肿瘤生长，而且与游离DOX相比，甚至与DOX-PMs和DOX-PMs + Cur相比，对心脏组织的病理损伤显著更小。总之，这种具有DOX和Cur的靶向组合胶束递送系统在肿瘤治疗中可能是一种有前途的载体。(C)© 2016 Elsevier B. V.版权所有。
Chemotherapeutic drugs have a series of limitations in anti-tumor treatment, mainly including multidrug resistance (MDR) and serious adverse reactions. Co-delivery system with two or more synergistic therapeutic drugs is an effective strategy to settle these limitations. In this study, active tumor-targeted co-delivery micelles (DOX + Cur)-PMs, with two synergistic drugs of a therapeutic drug of doxorubicin (DOX) and a chemosensitizer of curcumin (Cur) co-encapsulated into hyaluronic acid-vitamin E succinate (HA-VES) graft copolymer, were prepared and delivered simultaneously into tumor cells for improving therapeutic effects of DOX. (DOX + Cur)-PMs had uniform particle size, high encapsulation efficacy, sustained release profile and good colloidal stability. In vitro cytotoxicity study, (DOX + Cur)-PMs exerted the strongest cytotoxicity and highest cell apoptosis-inducing activities against DOX-resistant MCF-7/Adr cells. Moreover, (DOX + Cur)-PMs more efficiently internalized into cancer cells and enhanced the cellular uptake of DOX via energy-dependent and caveolae-mediated endocytosis, and significantly reversed MDR effects via CD44 targeting delivery and the synergic effect of released Cur. More importantly, in vivo results illustrated that (DOX + Cur)-PMs not only displayed better tumor accumulation and tumor targeting, and more efficiently inhibited the growth of tumor in 4T1 tumor-bearing mice, but also induced significantly less pathological damage to the cardiac tissue in comparison with free DOX, even DOX-PMs and DOX-PMs + Cur. In summary, this targeted combinational micellar delivery system with DOX and Cur could be a promising vehicle in tumor therapy. (C) 2016 Elsevier B.V. All rights reserved.