Construction of RGD10-NGR9 dual-targeting superparamagnetic iron oxide and its magnetic resonance imaging features in nude mice.
- Author:
Qiong-ya WU
1
;
Jing-yun SHI
;
Jie ZHANG
;
Lin-qian ZHANG
;
Yin-min ZHAO
;
Liang TANG
;
Yun CHEN
;
Xiao-dong HE
;
Hui LIU
;
Bo SU
2
Author Information
- Publication Type:Journal Article
- MeSH: Adenocarcinoma; diagnosis; metabolism; pathology; Aminopeptidases; analysis; Animals; Cell Line, Tumor; Cells, Cultured; Contrast Media; chemistry; Dextrans; chemistry; Ferrosoferric Oxide; metabolism; Human Umbilical Vein Endothelial Cells; cytology; metabolism; Humans; Integrin alphaVbeta3; analysis; Lung Neoplasms; diagnosis; metabolism; pathology; Magnetic Resonance Imaging; Magnetite Nanoparticles; chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Oligopeptides; chemistry; Particle Size; Signal-To-Noise Ratio
- From: Chinese Journal of Oncology 2013;35(11):808-813
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo construct angiogenesis-specific RGD10-NGR9 dual-targeting superparamagnetic iron oxide nanoparticles, and to evaluate its magnetic resonamce imaging (MRI) features in nude mice and potential diagnostic value in tumor MRI.
METHODSDual-targeting peptides RGD10-NGR9 were designed and synthesized. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were synthesized by chemical co-precipitation method and the surface was modified to be hydrophilic by coating with dextran. The dual-targeting peptides RGD10-NGR9 were conjugated to USPIO. Cell binding affinity and up-taking ability of the dual-targeting USPIO nanoparticles to integrin ανβ3-APN positive cells were subsequently tested by Prussian blue staining and phenanthroline colorimetry in vitro. The RGD10-NGR9 conjugated with USPIO was injected intravenously into xenograft mice, which were scanned by MRI at predetermined time points. The MRI and contrast-to-noise ratio (CNR) values were calculated to evaluate the ability of dual-targeting USPIO as a potential contrast agent in nude mice.
RESULTSP-CLN-Dextran-USPIO nanoparticles with stable physical properties were successfully constructed. The average diameter of Fe3O4 nanoparticles was 8-10 nm, that of Dextran-USPIO was about 20 nm and P-CLN-Dextran-USPIO had an average diameter about 30 nm. The in vitro studies showed a better specificity of dual-targeting USPIO nanoparticles on proliferating human umbilical vein endothelia cells (HUVEC). In vivo, RGD10-NGR9-USPIO showed a significantly reduced contrast in signal intensity and 2.83-times increased the CNR in the tumor MRI in xenograft mice.
CONCLUSIONThis novel synthesized RGD10-NGR9 dual-targeting USPIO is with better specific affinity in vitro and in vivo, and might be used as a molecular contrast agent for tumor angiogenesis MRI.