Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles
Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles
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通过可生物降解的聚合物胶束提高姜黄素的抗血管生成和抗肿瘤活性
DOI：
10.1016/j.biomaterials.2012.10.068
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发表时间：
2013-01-01
期刊：
影响因子：
14
通讯作者：
Wei, Yuquan
中科院分区：
文献类型：
--
作者：
Gong, Changyang;Deng, Senyi;Wei, Yuquan
为了开发姜黄素(Cur)的水溶液处方，提高其抗肿瘤活性，我们在不使用任何表面活性剂或有毒有机溶剂的情况下，采用固体分散法制备了Cur包埋的mpeg-PCL胶束。CuR胶束无需任何冻干剂或赋形剂即可冻干成粉末状，再溶解后的CuR胶束均匀稳定。分子模拟研究表明，CUR倾向于与PCL相互作用，以PCL为核心，以聚乙二醇为外壳。将Cur包裹到聚合物胶束中后，细胞毒性和细胞摄取均增加。CuR胶束对人脐静脉内皮细胞的增殖、迁移、侵袭和管状形成的抑制作用强于游离CuR。此外，在转基因斑马鱼模型中，CuR胶束表现出持续的体外释放行为和缓慢的血管外渗。在转基因斑马鱼模型中，CuR胶束显著抑制了胚胎血管生成和肿瘤诱导的血管生成。此外，在皮下和肺转移的LL/2肿瘤模型中，Cur胶束均能更有效地抑制肿瘤生长和延长生存期。在药代动力学和组织分布研究中，Cur胶束在血浆和肿瘤中具有较高的浓度和较长的滞留时间。我们的发现表明，CuR胶束在肺癌治疗中可能有很好的应用前景。(C)2012爱思唯尔有限公司。保留所有权利。
For developing aqueous formulation and improving anti-tumor activity of curcumin (Cur), we prepared Cur encapsulated MPEG-PCL micelles by solid dispersion method without using any surfactants or toxic organic solvent. Cur micelles could be lyophilized into powder form without any cryoprotector or excipient, and the re-dissolved Cur micelles are homogenous and stable. Molecular modeling study suggested that Cur tended to interact with PCL serving as a core embraced by PEG as a shell. After Cur was encapsulated into polymeric micelles, cytotoxicity and cellular uptake were both increased. Cur micelles had a stronger inhibitory effect on proliferation, migration, invasion, and tube formation of HUVECs than free Cur. Besides, Cur micelles showed a sustained in vitro release behavior and slow extravasation from blood vessels in transgenic zebrafish model. Embryonic angiogenesis and tumor-induced angiogenesis were both dramatically inhibited by Cur micelles in transgenic zebrafish model. Furthermore, Cur micelles were more effective in inhibiting tumor growth and prolonged survival in both subcutaneous and pulmonary metastatic LL/2 tumor models. In pharmacokinetic and tissue distribution studies, Cur micelles showed higher concentration and longer retention time in plasma and tumors. Our findings suggested that Cur micelles may have promising applications in pulmonary carcinoma therapy. (C) 2012 Elsevier Ltd. All rights reserved.