Fine-tuning vitamin E-containing telodendrimers for efficient delivery of gambogic acid in colon cancer treatment.
Fine-tuning vitamin E-containing telodendrimers for efficient delivery of gambogic acid in colon cancer treatment.
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DOI：
10.1021/acs.molpharmaceut.5b00051
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发表时间：
2015-04-06
影响因子：
4.9
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Huang W;Wang X;Shi C;Guo D;Xu G;Wang L;Bodman A;Luo J
某些天然产物如藤黄酸（GA）表现出有效的抗肿瘤作用。不幸的是，这些天然产物的给药受到它们在常规药物溶剂中溶解度差和毒副作用的限制。在这项研究中，一系列的telodendrimers，组成的线性聚乙二醇（PEG）的封闭树枝状低聚物的胆酸（CA）和维生素E（VE），已被设计与架构优化，有效地提供GA和其他天然抗癌化合物。两个telodendrimers与隔离CA和VE域自组装成稳定的圆柱形和/或球形纳米粒子（NP）后，加载GA的透射电子显微镜（TEM）下观察到，这与动态光散射（DLS）分析的子30 nm的颗粒尺寸。用优化的末端树枝状聚合物实现了非常高的GA负载容量（3：10药物/聚合物w/w）和持续的药物释放。发现GA的这些新型纳米制剂表现出与游离药物相似的针对结肠癌细胞的体外细胞毒性活性。近红外荧光小动物成像显示GA加载的NP优先积累到肿瘤组织中。优化的GA纳米制剂在HT-29人结肠癌异种移植物模型中与等效剂量的GA-Cremophor EL制剂相比实现了上级抗肿瘤功效。鉴于与这种天然化合物相关的轻微不良反应以及通过肿瘤靶向末端树枝状聚合物递送增强的抗癌作用，GA是结肠癌治疗中传统化疗的有希望的替代方案。
Certain natural products such as gambogic acid (GA) exhibit potent anti-tumor effects. Unfortunately, administration of these natural products is limited by their poor solubility in conventional pharmaceutical solvents and toxic side effects. In this study, a series of telodendrimers, composed of linear polyethylene glycol (PEG)-blocking-dendritic oligomer of cholic acid (CA) and vitamin E (VE), have been designed with architectures optimized for efficient delivery of GA and other natural anticancer compounds. Two of the telodendrimers with segregated CA and VE domains self-assembled into stable cylindrical and/or spherical nanoparticles (NPs) after being loaded with GA as observed under transmission electron microscopy (TEM), which correlated with the dynamic light scattering (DLS) analysis of sub-30 nm particle sizes. A very high GA loading capacity (3:10 drug/polymer w/w) and sustained drug release were achieved with the optimized telodendrimers. These novel nanoformulations of GA were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug. Near-infrared fluorescence small animal imaging revealed preferential accumulation of GA-loaded NPs into tumor tissue. The optimized nanoformulation of GA achieved superior anti-tumor efficacy compared to GA-Cremophor EL formulation at equivalent doses in HT-29 human colon cancer xenograft model. Given the mild adverse effects associated with this natural compound and the enhanced anticancer effects via tumor targeted telodendrimer delivery, GA is a promising alternative to the traditional chemotherapy in colon cancer treatment.
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用于紫杉醇和顺铂共递送的Telodendrimer纳米载体：一种用于卵巢癌治疗的协同组合纳米疗法。
影响因子：
14
作者：
Cai, Liqiong;Xu, Gaofei;Shi, Changying;Guo, Dandan;Wang, Xu;Luo, Juntao
通讯作者：
Luo, Juntao
影响因子：
16.6
作者：
Li, Yuanpei;Xiao, Wenwu;Xiao, Kai;Berti, Lorenzo;Luo, Juntao;Tseng, Harry P.;Fung, Gabriel;Lam, Kit S.
通讯作者：
Lam, Kit S.
影响因子：
4.1
作者：
Leznicki, Pawel;Warwicker, Jim;High, Stephen
通讯作者：
High, Stephen
影响因子：
3.7
作者：
Oerlemans C;Bult W;Bos M;Storm G;Nijsen JF;Hennink WE
通讯作者：
Hennink WE
影响因子：
4.9
作者：
Huang, Wenzhe;Shi, Changying;Luo, Juntao
通讯作者：
Luo, Juntao