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

Fan Zhang, Xinglu Huang, Lei Zhu, Ning Guo, Gang Niu, Magdalena Swierczewska, Seulki Lee, Hong Xu, Andrew Y. Wang, Khalid A. Mohamedali, Michael G. Rosenblum, Guangming Lu, Xiaoyuan Chen

Research output: Contribution to journalArticle

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 VEGF 121/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 α vβ 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 VEGF 121/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.

Original languageEnglish (US)
Pages (from-to)5414-5422
Number of pages9
JournalBiomaterials
Volume33
Issue number21
DOIs
StatePublished - Jul 1 2012
Externally publishedYes

Keywords

  • Iron oxide nanoparticles (IONPs)
  • Magnetic resonance imaging (MRI)
  • RGD peptides
  • Therapy response
  • Tumor targeting

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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  • Cite this

    Zhang, F., Huang, X., Zhu, L., Guo, N., Niu, G., Swierczewska, M., Lee, S., Xu, H., Wang, A. Y., Mohamedali, K. A., Rosenblum, M. G., Lu, G., & Chen, X. (2012). Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles. Biomaterials, 33(21), 5414-5422. https://doi.org/10.1016/j.biomaterials.2012.04.032