Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

• Published in: International journal of nanomedicine Vol. 11; pp. 5671 - 5682
• Main Authors: Cui, Yanfen, Zhang, Caiyuan, Luo, Ran, Liu, Huanhuan, Zhang, Zhongyang, Xu, Tianyong, Zhang, Yong, Wang, Dengbin
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2016; Dove Medical Press
• Subjects: Acrylic Resins - chemistry; Animals; antiangiogenic therapy; Aspartate; Cancer; Carcinoma; Cell Transformation, Neoplastic; Disease Models, Animal; Endostar; Female; Ferric oxide; Humans; Integrin alphaVbeta3 - metabolism; integrin avβ3; Integrins; Ionizing radiation; Iron compounds; Magnetic Resonance Imaging; Magnetite Nanoparticles - chemistry; Mice; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - blood supply; Nasopharyngeal Neoplasms - diagnostic imaging; Nasopharyngeal Neoplasms - pathology; Nasopharyngeal Neoplasms - therapy; Neovascularization, Pathologic; Oligopeptides - chemistry; Oligopeptides - metabolism; Original Research; Particle Size; Treatment Outcome; ultrasmall superparamagnetic iron oxide; antiangiogenic therapy; integrin αvβ3; magnetic resonance imaging; nasopharyngeal carcinoma; ultrasmall superparamagnetic iron oxide; Endostar
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S115357

Arginine-glycine-aspartic acid (RGD)-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA)-coated ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-PAA-USPIO) in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC) xenograft model by magnetic resonance imaging (MRI). The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs) was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group). The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 ( <0.05). This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in NPC xenograft model, favoring its potential clinical translation.