PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers.
PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers.
复制标题
DOI：
10.1016/j.biomaterials.2012.10.073
复制
发表时间：
2013-02
期刊：
影响因子：
14
通讯作者：
Li, Song
中科院分区：
文献类型：
--
作者：
Lu, Jianqin;Huang, Yixian;Zhao, Wenchen;Marquez, Rebecca T.;Meng, Xiaojie;Li, Jiang;Gao, Xiang;Venkataramanan, Raman;Wang, Zhou;Li, Song
紫杉醇（PTX）是治疗多种癌症最有效的化疗药物之一，但其治疗效果往往受到严重副作用的限制。我们开发了一种基于胶束的PTX制剂，该制剂基于衍生自聚乙二醇5000（PEG 5 K）和恩贝林（EB）的简单缀合物。Embelin是一种天然产物，通过阻断X连锁凋亡抑制蛋白（XIAP）的活性而发挥抗肿瘤活性。PEG 5 K-EB 2偶联物在水溶液中自组装形成稳定的胶束，并有效地包封疏水性药物，如PTX。PEG 5 K-EB 2胶束的CMC值为0.002mg/mL（0.35μM），粒径在20 ~ 30 nm之间，有或没有负载PTX。体外细胞摄取研究表明，PEG 5 K-EB 2胶束被肿瘤细胞有效地摄取。体外释放研究表明，紫杉醇在PEG 5 K-EB 2胶束中的释放速度比紫杉醇的释放速度慢得多，超过5天。在几种培养的肿瘤细胞系中，在PEG 5 K-EB 2胶束中配制的PTX表现出比紫杉醇更强的细胞毒性。全身近红外荧光（NIRF）成像显示，PEG 5 K-EB 2胶束选择性地积聚在肿瘤部位，在包括肝脏和脾脏在内的主要器官中摄取最少。载PTX的PEG 5 K-EB 2胶束表现出优异的安全性特征，在小鼠中的最大耐受剂量（MTD）为100-120 mg PTX/kg，其显著高于泰素（15-20 mg PTX/kg）。最后，在乳腺癌和前列腺癌的小鼠模型中，与紫杉醇相比，在PEG 5 K-EB 2胶束中配制的PTX显示出上级抗肿瘤活性。
Paclitaxel (PTX) is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its therapeutic benefit is often limited by severe side effects. We have developed a micelle-based PTX formulation based on a simple conjugate derived from polyethylene glycol 5000 (PEG5K) and embelin (EB). Embelin is a natural product and exhibits antitumor activity through blocking the activity of X-linked inhibitor of apoptosis protein (XIAP). PEG5K-EB2 conjugate self-assembles to form stable micelles in aqueous solution and efficiently encapsulates hydrophobic drugs such as PTX. PEG5K-EB2 micelles have a relatively low CMC of 0.002mg/mL (0.35μM) with sizes in the range of 20 ~ 30 nm with or without loaded PTX. In vitro cell uptake study showed that the PEG5K-EB2 micelles were efficiently taken up by tumor cells. In vitro release study showed that PTX formulated in PEG5K-EB2 micelles was slowly released over 5 days with much slower release kinetics than that of Taxol formulation. PTX formulated in PEG5K-EB2 micelles exhibited more potent cytotoxicity than Taxol in several cultured tumor cell lines. Total body near infrared fluorescence (NIRF) imaging showed that PEG5K-EB2 micelles were selectively accumulated at tumor site with minimal uptake in major organs including liver and spleen. PTX-loaded PEG5K-EB2 micelles demonstrated an excellent safety profile with a maximum tolerated dose (MTD) of 100–120 mg PTX/kg in mice, which was significantly higher than that for Taxol (15–20 mg PTX/kg). Finally, PTX formulated in PEG5K-EB2 micelles showed superior anti-tumor activity compared to Taxol in murine models of breast and prostate cancers.
登录
查看更多内容
影响因子：
4.9
作者：
Liu Y;Huang L;Liu F
通讯作者：
Liu F
DOI：
10.1016/j.jconrel.2010.02.027
发表时间：
2010-06-15
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Li Y;Xiao K;Luo J;Lee J;Pan S;Lam KS
通讯作者：
Lam KS
影响因子：
5.7
作者：
Husain K;Francois RA;Yamauchi T;Perez M;Sebti SM;Malafa MP
通讯作者：
Malafa MP
影响因子：
7.2
作者：
Holcik, M;Gibson, H;Korneluk, RG
通讯作者：
Korneluk, RG
DOI：
10.1016/j.ejpb.2009.06.015
发表时间：
2009-10-01
影响因子：
4.9
作者：
Danhier, Fabienne;Magotteaux, Nicolas;Preat, Veronique
通讯作者：
Preat, Veronique