Fabrication of {198Au0} radioactive composite nanodevices and their use for nanobrachytherapy

Khan, Mohamed K.; Minc, Leah D.; Nigavekar, Shraddha S.; Kariapper, Muhammed S.T.; Nair, Bindu M.; Schipper, Matthew; Cook, Andrew C.; Lesniak, Wojciech G.; Balogh, Lajos P.

doi:10.1016/j.nano.2007.11.005

« Previous Next »Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 1 , Pages 57-69, March 2008

Fabrication of {¹⁹⁸Au⁰} radioactive composite nanodevices and their use for nanobrachytherapy

Mohamed K. Khan, MD, PhD
- NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York
Leah D. Minc, PhD
- OSU Radiation Center, Oregon State University, Corvallis, Oregon
Shraddha S. Nigavekar, PhD
- Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan
Muhammed S.T. Kariapper, PhD
- NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York
Bindu M. Nair, PhD
- NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York
Matthew Schipper, PhD
- OSU Radiation Center, Oregon State University, Corvallis, Oregon
Andrew C. Cook, PhD
- Department of Nuclear Engineering, Burlington Engineering Laboratories, North Carolina State University, Raleigh, North Carolina, USA
Wojciech G. Lesniak, PhD
- NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York
Lajos P. Balogh, PhD
- NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York
- Corresponding author: NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA.

Received 11 April 2007; accepted 26 November 2007. published online 01 February 2008.

Abstract

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 μCi 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.