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Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice

Authors Smilowitz HM, Tarmu LJ, Sanders MM, Taylor JA III, Choudhary D, Xue C, Dyment NA, Sasso D, Deng X, Hainfeld JF

Received 3 May 2017

Accepted for publication 9 September 2017

Published 27 October 2017 Volume 2017:12 Pages 7937—7946


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Dr Thomas Webster

Henry M Smilowitz,1 Lauren J Tarmu,1–3 Mary Melinda Sanders,4 John A Taylor III,5 Dharamainder Choudhary,6 Crystal Xue,7 Nathaniel A Dyment,8 Dan Sasso,1 Xiaomeng Deng,9 James F Hainfeld10

1Department of Cell Biology, University of Connecticut Health Center, Farmington, CT, 2Department of Human Behavior, College of Southern Nevada, North Las Vegas, 3Department of Anthropology, University of Nevada, Las Vegas, NV, 4Department of Anatomic Pathology, University of Connecticut Health Center, Farmington, CT, 5Department of Urology, University of Kansas Medical Center, Kansas City, KS, 6Department of Surgery, University of Connecticut Health Center, Farmington, CT, 7George Washington University School of Medicine, Washington, DC, 8Department of Orthopedic Surgery, University of Pennsylvania, Philadelphia, PA, 9David Geffen School of Medicine at UCLA, Los Angeles, CA, 10Nanoprobes, Inc, Yaphank, NY, USA

Abstract: Bladder-sparing options are being developed for muscle-invasive bladder cancer in place of radical cystectomy, including the combination of chemotherapy and radiation therapy. We reasoned that improving the radiotherapy component of chemoradiation could improve the control of locally advanced disease. Previously, we showed that gold nanoparticles (AuNPs) are potent enhancers of radiation therapy. We hypothesized that if AuNPs were to preferentially localize to bladder tumors, they may be used to enhance the radiation component of muscle-invasive bladder tumor therapy. Mice were treated with the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 17, 20, and 22 weeks – long enough to induce muscle-invasive tumors. Mice were then anesthetized and injected intravenously with 1.9 nm AuNPs of which most were rapidly cleared from the blood and excreted after a 30–50 minute residence time in the bladder. We found AuNPs distributed throughout the bladder wall, but most of the AuNPs were associated with the stroma surrounding the tumor cells or extracellular keratin produced by the tumor cells. There were relatively few AuNPs in the tumor cells themselves. The AuNPs therefore localized to tumor-associated stroma and this tumor specificity might be useful for specific X-ray dose enhancement therapy of muscle-invasive bladder carcinomas.

Keywords: N-butyl-N-(4-hydroxybutyl)nitrosamine, BBN, muscle-invasive bladder cancer, gold nanoparticles, mouse model

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