[Construction of RGD10-NGR9 dual-targeting superparamagnetic iron oxide and its magnetic resonance imaging features in nude mice].
OBJECTIVE
To 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.


METHODS
Dual-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.


RESULTS
P-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.


CONCLUSIONS
This 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.
Department of Radiation Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433, China.
Qiong-ya
QY
Wu
Jing-yun
JY
Shi
Jie
J
Zhang
Lin-qian
LQ
Zhang
Yin-min
YM
Zhao
Liang
L
Tang
Yun
Y
Chen
Xiao-dong
XD
He
Hui
H
Liu
Email: su_bo_s@hotmail.com.
Bo
B
Su
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000626:Aminopeptidases / Q000032:analysis; D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry; D003911:Dextrans / Q000737:chemistry; D052203:Ferrosoferric Oxide / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000737:chemistry; D010316:Particle Size; D059629:Signal-To-Noise Ratio
D003287:Contrast Media; D003911:Dextrans; D039302:Integrin alphaVbeta3; D058185:Magnetite Nanoparticles; C526428:NGR peptide; D009842:Oligopeptides; C097921:ferumoxtran-10; C047981:arginyl-glycyl-aspartic acid; D000626:Aminopeptidases; D052203:Ferrosoferric Oxide