Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer.
J Drug Target. 2015 ;23(6):568-76. Epub 2015 Mar 4. PMID: 25738990
BACKGROUND: Multifunctional gold nanospheres (MGNs)-loaded with docetaxel ([email protected]) were prepared and evaluated for therapeutic efficacy in nude mice bearing human prostate cancer xenografts.
METHODS: MGNs were prepared from PEGylated hollow gold nanospheres (HGNs) coated with folic acid and DTPTT chelate. Then, the effect of radiolabelled MGNs ((99m)Tc-MGNs) on PC-3 cell apoptosis was assessed by flow cytometry, while their binding affinity to these cells was evaluated by cell binding assays. Next, biodistribution of (99m)Tc-MGNs in xenograft bearing mice was measured by SPECT imaging. Also, DTX loading and release rates were estimated in [email protected] Finally, in vitro stability in human serum and cytotoxicity of [email protected] were assessed, as well as their antitumor effect in xenograft bearing mice.
RESULTS: (99m)Tc-MGNs (97.69% purity) showed good binding affinity to PC-3 cells, a specific recognition blocked by excess folic acid. Interestingly, [email protected] remained stable in human serum for 24 h, and exhibited higher mean cytotoxicity after NIR laser irradiation than free DTX. By day 28, tumor inhibition rates were higher in the [email protected] + NIR laser irradiation group compared with the DTX and MGNs + NIR laser irradiation groups.
CONCLUSIONS: Loading chemotherapeutic drugs into MGNs can increase antitumor potency, reduce normal cell damage and decrease drug resistance, thus representing a promising approach for advanced prostate cancer treatment.