Fabrication of {198Au0} radioactive composite nanodevices and their use for nanobrachytherapy.
We describe the simple fabrication of poly({198Au}) radioactive gold-dendrimer composite nanodevices in distinct sizes (diameter between 10 nm and 29 nm) for targeted radiopharmaceutical dose delivery to tumors in vivo. Irradiation of aqueous solutions of 197Au containing poly(amidoamine) dendrimer tetrachloroaurate salts or {197Au0} gold-dendrimer nanocomposites in a nuclear reactor resulted in the formation of positively charged and soluble poly{198Au0} radioactive composite nanodevices (CNDs). A mouse melanoma tumor model was used to test whether the poly{198Au0} CNDs can deliver a therapeutic dose. A single intratumoral injection of poly{198Au0}(d=22nm) CNDs in phosphate-buffered saline delivering a dose of 74 muCi resulted after 8 days in a statistically significant 45% reduction in tumor volume, when compared with untreated groups and those injected with the "cold" nanodevice. No clinical toxicity was observed during the experiments. This study provides the first proof of principle that radioactive CNDs can deliver therapeutic doses to tumors.
Khan
Mohamed K
MK
NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Minc
Leah D
LD
Nigavekar
Shraddha S
SS
Kariapper
Muhammed S T
MS
Nair
Bindu M
BM
Schipper
Matthew
M
Cook
Andrew C
AC
Lesniak
Wojciech G
WG
Balogh
Lajos P
LP
D001918:Brachytherapy / Q000295:instrumentation*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D050091:Dendrimers; D004591:Electrophoresis, Polyacrylamide Gel; D006050:Gold Radioisotopes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures; D011073:Polyamines; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D050091:Dendrimers; D006050:Gold Radioisotopes; C104700:PAMAM Starburst; D011073:Polyamines