In vitro and in vivo evaluation of APRPG-modified angiogenic vessel targeting micelles for anticancer therapy
In vitro and in vivo evaluation of APRPG-modified angiogenic vessel targeting micelles for anticancer therapy
复制标题
APRPG 修饰的血管生成血管靶向胶束用于抗癌治疗的体外和体内评估
DOI：
10.1016/j.ijpharm.2015.03.067
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发表时间：
2015-05-30
影响因子：
5.8
通讯作者：
Pan, Weisan
中科院分区：
文献类型：
--
作者：
Guo, Pan;Song, Shuangshuang;Pan, Weisan
以紫杉醇（PTX）为模型药物，将血管生成导向肽APRPG与两亲性共聚物PLGA-PEG偶联，制备紫杉醇血管导向胶束（APRPG-PEG-Mic），评价APRPG修饰血管导向药物载体的抗肿瘤作用。胶束呈均匀球形，粒径分布呈单峰，Zeta电位略负。体外释药结果表明，APRPG-PEG-Mic具有明显的缓释性能。与Taxol（R）和Cont-PEG-Mic相比，APRPG-PEG-Mic对两种癌细胞系显示出更强的细胞毒性。在细胞摄取研究中，APRPG修饰的胶束增强了EA的细胞内荧光强度。hy 926细胞。生物分布研究表明，APRPG-PEG-Mic在肿瘤组织中的蓄积是被动蓄积和主动靶向的结果。与Taxol（R）和Cont-PEG-Mic相比，APRPG-PEG-Mic能显著减小肿瘤体积，延长荷瘤小鼠的生存时间，表明APRPG-PEG-Mic具有更高的抗肿瘤疗效和更低的系统性副作用。(C)2015爱思唯尔B. V.保留所有权利。
The study was aimed to evaluate the antitumor potential of the Ala-Pro-Arg-Pro-Gly (APRPG)-modified angiogenic vessel targeting drug delivery system using paclitaxel (PTX) as a model drug.In this study, an angiogenesis homing peptide APRPG was conjugated to the amphipathic copolymer PLGA-PEG and the synthesized copolymer APRPG-PEG-PLGA was used to prepare PTX encapsulated micelles (APRPG-PEG-Mic). The micelles were uniform spherical and exhibited a unimodal particle size distribution and a slight negative zeta-potential. The in vitro drug release result demonstrated a significant sustained release property of APRPG-PEG-Mic. Compared to Taxol (R) and Cont-PEG-Mic, APRPG-PEG-Mic showed a stronger cytotoxicity against two cancerous cell lines. In the cell uptake studies, the APRPG-modified micelles enhanced intracellular fluorescent intensity in EA. hy926 cells. The biodistribution study revealed the accumulation of APRPG-PEG-Mic in tumor tissues as a result of passive accumulation and active targeting. In comparison with Taxol (R) and Cont-PEG-Mic, APRPG-PEG-Mic reduced the tumor volume more significantly and prolonged the survival time of tumor-bearing mice, indicating a higher antitumor efficacy and lower systematic side effects of APRPG-PEG-Mic.The results indicated that APRPG-modified micelles could be an efficient target-delivery method to angiogenic vessels and a highly promising therapeutic system in anticancer therapy. (C) 2015 Elsevier B.V. All rights reserved.