Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer.
BACKGROUND
Multifunctional gold nanospheres (MGNs)-loaded with docetaxel (MGN@DTX) 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 MGN@DTX. Finally, in vitro stability in human serum and cytotoxicity of MGN@DTX 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, MGN@DTX 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 MGN@DTX + 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.
Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , P.R. China .
Yanfang
Y
Shen
Zhiya
Z
Ma
Fei
F
Chen
Qingjian
Q
Dong
Qiran
Q
Hu
Lingyu
L
Bai
Jing
J
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D065546:Drug Liberation; D004355:Drug Stability; D006046:Gold / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D051379:Mice; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry*; D010778:Photochemotherapy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D011869:Radioligand Assay; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D013667:Technetium; D006046:Gold
Docetaxel; gold nanospheres; near-infrared laser; prostate cancer