Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles

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• 作者：Fan Zhang^a ; ¹ ; Xinglu Huang^b ; ¹ ; Lei Zhu^b ; ^c ; Ning Guo^c ; Gang Niu^b ; Magdalena Swierczewska^b ; Seulki Lee^b ; Hong Xu^d ; Andrew Y. Wang^d ; Khalid A. Mohamedali^e ; Michael G. Rosenblum^e ; Guangming Lu^a ; ^{cjr.luguangming@vip.163.com} ; Xiaoyuan Chen^b ; ^c ; ^{shawn.chen@nih.gov}
• 关键词：Magnetic resonance imaging (MRI) ; Iron oxide nanoparticles (IONPs) ; RGD peptides ; Tumor targeting ; Therapy response
• 刊名：Biomaterials
• 出版年：2012
• 期刊代码：7_01429612
• 类别：ms
• 出版时间：July, 2012
• 卷：33
• 期：21
• 页码：5414-5422
• 文件大小：1760 K

摘要

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聽vitro binding assays confirmed that cellular uptake of particles was mainly dependent on the interaction between RGD and integrin 伪_v尾₃ 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.