title: Noninvasive monitoring of orthotopic glioblastoma therapy response using RGD-conjugated iron oxide nanoparticles.
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(v)β(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.
authors.affiliation: Department of Radiology, Nanjing Jinling Hospital, Clinical School of Medical College of Nanjing University, Nanjing 210002, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Xinglu
authors.initials: X
authors.lastname: Huang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
authors.forename: Ning
authors.initials: N
authors.lastname: Guo
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Magdalena
authors.initials: M
authors.lastname: Swierczewska
authors.forename: Seulki
authors.initials: S
authors.lastname: Lee
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Wang
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Mohamedali
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenblum
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009389:Neovascularization, Pathologic / Q000378:metabolism; D009842:Oligopeptides / Q000737:chemistry; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D013194:Staining and Labeling; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D005290:Ferric Compounds; D039302:Integrin alphaVbeta3; D039661:Integrin beta3; D009842:Oligopeptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C000499:ferric oxide; C047981:arginyl-glycyl-aspartic acid