iRGD-mediated core-shell nanoparticles loading carmustine and O6-benzylguanine for glioma therapy
iRGD-mediated core-shell nanoparticles loading carmustine and O6-benzylguanine for glioma therapy
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DOI：
10.1080/1061186x.2016.1238091
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发表时间：
2017-01-01
影响因子：
4.5
通讯作者：
Jiang, Yanyan
中科院分区：
文献类型：
--
作者：
Chang, Liu;Sen Yao;Jiang, Yanyan
据报道，对α m整联蛋白具有高亲和力的iRGD（内化RGD）通过结合神经纤毛蛋白-1（NRP-1）来增强肿瘤穿透性。基于我们之前的研究，负载卡莫司汀（BCNU）及其增敏剂（O-6-苄基鸟嘌呤，BG）的壳聚糖表面修饰聚（丙交酯-乙交酯）纳米颗粒（PLGA/ CS NPs）比游离药物表现出更强的抗肿瘤作用。本研究制备了具有核-壳结构的PLGA/ CS纳米粒（NPs），并对其进行了iRGD或mPEG修饰。选择具有不同受体水平的F98、C6或U87细胞系用于体外和体内研究。在施用iRGD介导的NP（包括iRGD修饰的NP（iRGD-NP））和共同施用iRGD和NP（iRGD_NP）后，将它们对胶质瘤的作用与NP进行比较。iRGD-NP显示出比其他组更强的细胞毒性和细胞摄取。iRGD-NPs和iRGD_NPs在三维（3D）胶质瘤球体上显示出比NPs更深的肿瘤穿透和更强的抗侵袭作用。在F98荷瘤小鼠模型上，iRGD介导的NPs显示出增强的穿过BBB能力和脑肿瘤蓄积水平。相应地，iRGD_NP、iRGD-NP和NP组的中位生存时间分别为58、49和34.5天。目前的研究支持iRGD介导的策略，以提高抗肿瘤药物输送系统的功效。重要的是，iR ⑶的共同施用可能是比iR ⑶的缀合更好的方式。
iRGD (internalizing RGD) with high affinity to am integrins was reported to enhance tumor penetrability by binding to neuropilin-1 (NRP-1). Based on our previous study, chitosan surface-modified poly (lactide-coglycolides) nanoparticles (PLGA/ CS NPs), loaded with carmustine (BCNU) and its sensitizer (O-6-benzylguanine, BG) showed stronger anti-tumor effect than free drugs. In present study, PLGA/ CS NPs (NPs) with core-shell structure were prepared and modified with iRGD or mPEG. F98, C6 or U87 cell lines with different receptors levels were selected for in vitro and in vivo studies. After administration of iRGD-mediated NPs, including iRGD-modified NPs (iRGD-NPs) and co-administration of iRGD and NPs (iRGD_NPs), their effects on glioma were compared with NPs. iRGD-NPs showed stronger cytotoxicity and cellular uptake than other groups. iRGD-NPs and iRGD_NPs displayed deeper tumor penetration and stronger anti-invasion effect on three dimensional (3D) glioma spheroids than NPs. On F98 glioma-bearing mice model, iRGD-mediated NPs showed enhanced crossing BBB ability and brain tumor accumulation levels. Correspondingly, the median survival time of iRGD_NPs, iRGD-NPs and NPs groups were 58, 49 and 34.5 days, respectively. Present studies supported the iRGD-mediated strategy to improve the efficacy of antitumor drug delivery system. Importantly, co-administration of iRGD may be a greater way over the conjugation of iRGD.