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/CD 13).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.
ABSTRACT
Objective To develop a fluorescence signal activatable multifunctional molecular probe with theranostics function through combining ultrasmall gold nanorods(UGNRs) with fluorescein,and to evaluate its therapeutic effect on photothermal therapy (PTT) in breast cancer cells.Methods The UGNRs were synthesized by the one-pot seedless method,then the functionalized modification of UGNRs were conducted using cysteamine.Finally,the activatable ultrasmall gold nanorods (AUGNRs) were synthesized by amide condensation of —NH2 of cysteamine and —COOH of carboxylated fluorescein CyS.The cell uptake ability and GSH-mediated imaging ability of AUGNRs were studied using breast cancer 4T1 cells.4T1 cells co-cultured with AUGNRs were irradiated with 808 nm excitation light,and the PTT effects were assessed by MTT colorimetric staining and calcein-AM/PI staining.Results The AUGNRs were synthesized successfully,which could be uptaken by 4T1 cells quickly and efficiently,and could achieve intracellular glutathione (GSH) triggered fluorescence recovery.No obvious cytotoxicity of AUGNRs to 4T1 cells was observed in the co-cultivation.Moreover,obvious PTT effects could be induced by 808 nm laser,which could effectively kill 4T1 cancer cells.Conclusion The fluorescence signals of AUGNRs can be induced by intracellular GSH,and tumor cell destruction can be achieved by 808 laser-excitated PTT effects.