Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles.
Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles.
复制标题
使用 RGD 结合的氧化铁纳米粒子无创监测原位胶质母细胞瘤治疗反应。
DOI：
10.1016/j.biomaterials.2012.04.032
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发表时间：
2012-07
期刊：
影响因子：
14
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Zhang, Fan;Huang, Xinglu;Zhu, Lei;Guo, Ning;Niu, Gang;Swierczewska, Magdalena;Lee, Seulki;Xu, Hong;Wang, Andrew Y.;Mohamedali, Khalid A.;Rosenblum, Michael G.;Lu, Guangming;Chen, Xiaoyuan
关键词：
无创性成像技术已被认为是临床上监测肿瘤对治疗的早期反应的重要策略。在本研究中，我们将RGD肽与氧化铁纳米颗粒（IONP-RGD）结合作为磁共振成像（MRI）中的造影剂，以非侵入性地监测血管破坏剂VEGF 121/rGel在原位胶质母细胞瘤模型中的反应。首先将RGD肽偶联到用交联的PEG化的两亲性三嵌段共聚物包被的IONP上。体外结合实验证实，细胞对颗粒的摄取主要依赖于RGD与人脐静脉内皮细胞（HUVEC）整合素αvβ3之间的相互作用。在原位U87胶质母细胞瘤模型中观察到IONP-RGD的肿瘤靶向性。最后，使用IONP-RGD作为MRI的造影剂成功地实现了在治疗的早期阶段对VEGF 121/rGel治疗的肿瘤反应的非侵入性监测，这是一种优于基于肿瘤大小测量的常见解剖方法的上级方法。这项临床前研究可以加速抗癌药物的开发，促进纳米探针的临床转化。
Noninvasive imaging techniques have been considered important strategies in the clinic to monitor tumor early response to therapy. In the present study, we applied RGD peptides conjugated to iron oxide nanoparticles (IONP-RGD) as contrast agents in magnetic resonance imaging (MRI) to noninvasively monitor the response of a vascular disrupting agent VEGF121/rGel in an orthotopic glioblastoma model. RGD peptides were firstly coupled to IONPs coated with a crosslinked PEGylated amphiphilic triblock copolymer. In vitro binding assays confirmed that cellular uptake of particles was mainly dependent on the interaction between RGD and integrin αvβ3 of human umbilical vein endothelial cells (HUVEC). The tumor targeting of IONP-RGD was observed in an orthotopic U87 glioblastoma model. Finally, noninvasive monitoring of the tumor response to VEGF121/rGel therapy at early stages of treatment was successfully accomplished using IONP-RGD as a contrast agent for MRI, a superior method over common anatomical approaches which are based on tumor size measurements. This preclinical study can accelerate anticancer drug development and promote clinical translation of nanoprobes.
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