Application of cNGR functionalized gold nanoparticle probe in CT imaging of breast cancer angiogenesis

Abstract

Objective To prepare polyethylene glycol/cyclic asparagines-glycine-arginine functionalized gold nanoparticles (GNPs-PEG@cNGR) and evaluate their effectiveness in CT imaging of breast cancer angiogenesis. Methods The GNPs were synthesized by one-step reduction of chloroauric acid by sodium citrate. The thiolated PEG and cysteine-modified cNGR were coupled to the surface of GNPs through Au-S bonds, respectively. The GNPs-PEG@cNGR was characterized by transmission electron microscopy, Zeta potential/hydration particle size analyzer, and Fourier transform infrared spectrometer. The uptake and CT imaging effect of GNPs-PEG@cNGR were assessed by human umbilical vein endothelial cells (HUVEC) and human hepatoma cells (HepG2) positively expressed for aminopeptidase N (APN/CD13). The in vivo CT imaging effects on tumor angiogenesis and biocompatibility in mice of GNPs-PEG@cNGR were studied by BALB/c mouse model of 4T1 breast cancer. Results A specific CT molecular probe, i.e. GNPs-PEG@cNGR, was successfully constructed, which can target angiogenesis. The probe was spherical, with a hydration particle size of (35.7±1.0) nm and a Zeta potential of (-13.54±1.12) mV, and had good stability and biocompatibility. The GNPs-PEG@cNGR has good CT imaging results and can specifically target CD13-positive HUVEC and HepG2 cells. The CT imaging results in 4T1 breast cancer mice indicated that GNPs-PEG@cNGR could be specifically enriched in the tumor tissue after injection. The CT value of tumors in GNPs-PEG@cNGRz group was higher than that of GNPs-PEG group, and the difference was statistically significant (P<0.05). Conclusions GNPs-PEG@cNGR can specifically target CD13 positive cells and can be used as a CT contrast agent for imaging tumor angiogenesis. Key words: Cyclic asparagines-glycine-arginine; Gold nanoparticles; Breast cancer; Tumor angiogenesis; CT imaging