Specific targeting of angiogenesis in lung cancer with RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a 4.7T magnetic resonance scanner.
- Author:
Can LIU
1
;
Dong-Bo LIU
;
Guo-Xian LONG
;
Jun-Feng WANG
;
Qi MEI
;
Guang-Yuan HU
;
Hong QIU
;
Guo-Qing HU
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cells, Cultured; Dextrans; therapeutic use; Humans; Integrin alphaVbeta3; analysis; Lung Neoplasms; blood supply; drug therapy; Magnetic Resonance Imaging; Magnetite Nanoparticles; therapeutic use; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic; prevention & control; Oligopeptides; therapeutic use
- From: Chinese Medical Journal 2013;126(12):2242-2247
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDAngiogenesis is an essential step for tumor development and metastasis. The cell adhesion molecule avβ3 integrin plays an important role in angiogenesis and is a specific marker of tumor angiogenesis. A novel avβ3 integrin- targeted magnetic resonance (MR) imaging contrast agent utilizing Arg-Gly-Asp (RGD) and ultrasmall superparamagnetic iron oxide particles (USPIO) (referred to as RGD-USPIO) was designed and its uptake by endothelial cells was assessed both in vitro and in vivo to evaluate the angiogenic profile of lung cancer.
METHODSUSPIO were coated with -NH3+ and conjugated with RGD peptides. Prussian blue staining was performed to evaluate the specific uptake of RGD-USPIO by human umbilical vein endothelial cells (HUVECs). Targeted uptake and subcellular localization of RGD-USPIO in HUVECs were confirmed by transmission electron microscopy (TEM). The ability of RGD-USPIO to noninvasively assess avβ3 integrin positive vessels in lung adenocarcinoma A549 tumor xenografts was evaluated with a 4.7T MR scanner. Immunohistochemistry was used to detect avβ3 integrin expression and vessel distribution in A549 tumor xenografts.
RESULTSHUVECs internalized RGD-USPIO significantly more than plain USPIO. The uptake of RGD-USPIO by HUVECs could be competitively inhibited by addition of free RGD. A significant decrease in T2 signal intensity (SI) was observed at the periphery of A549 tumor xenografts at 30 minutes (P < 0.05) and 2 hours (P < 0.01) after RGD-USPIO was injected via the tail vein. Angiogenic blood vessels were mainly distributed in the periphery of tumor xenografts with positive avβ3 integrin expression.
CONCLUSIONSRGD-USPIO could specifically label avβ3 integrin and be taken up by HUVECs. This molecular MR imaging contrast agent can specifically evaluate the angiogenic profile of lung cancer using a 4.7T MR scanner.