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

• Published in: Biomaterials 2012-07, Vol.33 (21), p.5414-5422
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; antineoplastic agents; Cell Line, Tumor; composite polymers; crosslinking; Dentistry; Disease Models, Animal; Female; Ferric Compounds - chemistry; Glioblastoma - blood supply; Glioblastoma - drug therapy; human umbilical vein endothelial cells; Human Umbilical Vein Endothelial Cells - metabolism; Humans; image analysis; Integrin alphaVbeta3 - metabolism; Integrin beta3 - metabolism; integrins; Iron oxide nanoparticles (IONPs); iron oxides; magnetic resonance imaging; Magnetic resonance imaging (MRI); Magnetic Resonance Imaging - methods; Mice; Mice, Nude; monitoring; nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Neovascularization, Pathologic - metabolism; Oligopeptides - chemistry; peptides; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; RGD peptides; Staining and Labeling; therapeutics; Therapy response; Tumor targeting; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor A - therapeutic use
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2012.04.032

Abstract 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 αv β3 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.