Glioma therapy using tumor homing and penetrating peptide-functionalized PEG-PLA nanoparticles loaded with paclitaxel
Glioma therapy using tumor homing and penetrating peptide-functionalized PEG-PLA nanoparticles loaded with paclitaxel
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使用肿瘤归巢和负载紫杉醇的穿透肽功能化 PEG-PLA 纳米颗粒进行神经胶质瘤治疗
DOI：
10.1016/j.biomaterials.2013.04.025
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发表时间：
2013-07-01
期刊：
影响因子：
14
通讯作者：
Chen, Jun
中科院分区：
文献类型：
--
作者：
Hu, Quanyin;Gao, Xiaoling;Chen, Jun
利用神经纤毛蛋白（neuropilin，NRP）在胶质瘤细胞和血管内皮细胞表面过度表达的特点，将具有高亲和力的NRP配体- tLyp-1肽（（R/K）XX（R/K））功能化到PEG-PLA纳米粒表面（tLyp-1-NP）介导其肿瘤归巢、血管外渗和深入渗透到胶质瘤实质中。tLyp-1-NP通过马来酰亚胺-硫醇偶联反应制备，在TEM下具有均匀的球形形状，粒径为111.30 +/- 15.64 nm。tLyp-1-NP在人脐静脉内皮细胞和大鼠C6神经胶质瘤细胞中均表现出增强的细胞摄取，增加的负载PTX的细胞毒性，以及改善的无血管C6神经胶质瘤球体中的渗透和生长抑制。通过体内成像和胶质瘤分布分析证实了tLyp-1-NP在胶质瘤部位的选择性积累和深度渗透。用PTX负载的tLyp-1-NP治疗的那些携带颅内C6胶质瘤的小鼠获得了最长的存活。本文的研究结果强烈表明，tLyp-1肽功能化的纳米颗粒DDS可以显着提高紫杉醇胶质瘤治疗的疗效。(C)2013爱思唯尔有限公司保留所有权利。
By taking advantage of the excessively upregulated expression of neuropilin (NRP) on the surface of both glioma cells and endothelial cells of angiogenic blood vessels, the ligand of NRP with high affinity - tLyp-1 peptide, which also contains a CendR motif ((R/K)XX(R/K)), was functionalized to the surface of PEG -PLA nanoparticles (tLyp-1-NP) to mediate its tumor homing, vascular extravasation and deep penetration into the glioma parenchyma. The tLyp-1-NP was prepared via a maleimide-thiol coupling reaction with uniformly spherical shape under TEM and particle size of 111.30 +/- 15.64 nm. tLyp-1-NP exhibited enhanced cellular uptake in both human umbilical vein endothelial cells and Rat C6 glioma cells, increased cytotoxicity of the loaded PTX, and improved penetration and growth inhibition in avascular C6 glioma spheroids. Selective accumulation and deep penetration of tLyp-1-NP at the glioma site was confirmed by in vivo imaging and glioma distribution analysis. The longest survival was achieved by those mice bearing intracranial C6 glioma treated with PTX-loaded tLyp-1-NP. The findings here strongly indicate that tLyp-1 peptide-functionalized nanoparticulate DDS could significantly improve the efficacy of paclitaxel glioma therapy. (C) 2013 Elsevier Ltd. All rights reserved.