Effective Photothermal Chemotherapy using Docetaxel-Loaded Gold Nanospheres that Target Advanced Prostate Cancer

Objectives the multifunctional gold nanosphere with loaded docetaxel (MGN@DTX) was constructed, and the theraoeutic efficacy was evaluated in nude mice bearing human prostate cancer xenograft.

Methods Hollow gold nanosphere (HGN) was synthesized by sacrificial galvanic replacement of cobalt in the presence of chloroauric acid.PEGylated HGN was constructed bearing folic acid and DTPTTchelate on its surfacegold sulfide bond, and then radiolabelled by ^99mTc. The effect of ^99mTc-MGN-induced PC-3 cell apoptosis was observed by flow cytometry,and the binding affinity of ^99mTc-MGN to PC-3 cells was evaluated by cell binding assay. SPECT imaging was performed to measure the biodisrtribution of ^99mTc-MGN in the nude mice bearing PC-3 prostate cancer xenograft. DTX release and loading was estimated in MGN@DTX. In vitro human serum stability and cytotoxicity of MGN@DTX was detected. Anti-tumor effect of MGN@DTX was analyzed in the nude mice bearing PC-3 prostate cancer xenograft.

Results HGN had average diameter of 46±4.8 nm and average Au shell thickness of 4.0 nM with the surface plasmon resonance peak of 798nm. ^99mTc-MGN has a good binding affinity to PC-3 cells, and its specific recognition was blocked by excessive amouts of folic acid. MGN@DTX with NIR laser irradiation exhibited higher maximum cytotoxicity than free DTX after 72 h incubation (P＜0.05).By the planned end point of day 28, the tumor inhibition rates in the group of MGN@DTXwith NIR laser irradiation were higher than those of the DTX group and the group of MGN with NIR laser irradiation (P＜0.05). And there was no significant difference in weight loss among the four groups (P＞0.05).

Conclusions MGN@DTX integrated photothermal ablation mediated by MGN with antitumor activity of DTX. It is expected to increase the potential of killing tumor cells of chemotherapeutic drugs, reduce the damage to normal cells and overcome the resistance. And it may be a promising approach to the treatment of advanced prostate cancer.

Research Support This work was supported by the National Natural Science Foundation of China (No. 81201117)