Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles
Anti-tumor activity of paclitaxel through dual-targeting carrier of cyclic RGD and transferrin conjugated hyperbranched copolymer nanoparticles
复制标题
环状RGD和转铁蛋白共轭超支化共聚物纳米颗粒双靶向载体的紫杉醇抗肿瘤活性
DOI：
10.1016/j.biomaterials.2011.11.012
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发表时间：
2012-02-01
期刊：
影响因子：
14
通讯作者：
Wu, Yan
中科院分区：
文献类型：
--
作者：
Xu, Qing;Liu, Yuexian;Wu, Yan
有针对性的交付战略正变得越来越重要。本文合成了一种新型超支化两亲性聚[（胺-酯）-co-（D，L-丙交酯）]/1，2-二棕榈酰-sn-甘油基-3-磷酸乙醇胺共聚物（HPAE-co-PLA/DPPE），其外周分别含有RGD肽（cRGDfK）和转铁蛋白（If），并用于制备紫杉醇双靶向化疗纳米粒（NPs）。这些纳米颗粒显示出令人满意的尺寸分布，高包封效率和pH依赖性释放曲线。超支化共聚物的固有荧光使得在体外和体内方便地检测和追踪纳米颗粒。体外细胞毒性研究证明，cRGDfK的存在使delta（v）beta（3）整合素过表达的人脐静脉内皮细胞的细胞毒性效率提高10倍，而If使If受体过表达的人宫颈癌细胞的细胞毒性提高2倍。载药纳米粒可以有效地转运到血管内皮细胞和靶肿瘤细胞中。这些结果表明，cRGDfK和If修饰的HPAE-co-PLA/DPPE可以通过受体介导的内吞作用在细胞内特异性地递送化疗剂，具有更大的功效。因此，这种由非细胞毒性和可生物降解的聚合物制备的荧光纳米载体在肿瘤治疗中的药物递送是有希望的。(C)2011爱思唯尔有限公司保留所有权利。
Targeted delivery strategies are becoming increasingly important. Herein, a novel hyperbranched amphiphilic poly[(amine-ester)-co-(D,L-lactide)]/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (HPAE-co-PLA/DPPE) with RGD peptide (cRGDfK) and transferrin (If) on the periphery was synthesized and used to prepare paclitaxel-loaded nanoparticles (NPs) for dual-targeting chemotherapy. These NPs show satisfactory size distribution, high encapsulated efficiency and a pH-dependent release profile. The intrinsic fluorescence of the hyperbranched copolymer renders the detection and tracking of NPs in vitro and in vivo conveniently. In vitro cytotoxicity studies proved that the presence of cRGDfK enhanced the cytotoxic efficiency by 10 folds in delta(v)beta(3) integrin over-expressed human umbilical vein endothelial cells, while If improved cytotoxicity by 2 folds in If receptor over-expressed human cervical carcinoma cells. The drug-loaded NPs can be efficiently transported into the vascular endothelial cells and the target tumor cells. These results indicate that the cRGDfK and If decorated HPAE-co-PLA/DPPE could deliver chemotherapies specifically inside the cell via receptor-mediated endocytosis with greater efficacy. Therefore, such a fluorescent nanocarrier prepared from non-cytotoxic and biodegradable polymers is promising for drug delivery in tumor therapy. (C) 2011 Elsevier Ltd. All rights reserved.