Photoacoustic imaging of clofazimine hydrochloride nanoparticle accumulation in cancerous vs normal prostates

• DOI: 10.1371/journal.pone.0219655
• Publication Date: 2019-07-15T17:40:05Z
• Authors: Joel W. Y. Tan; Mikhail D. Murashov; Gus R. Rosania; Xueding Wang
• Keywords: Male; 0301 basic medicine; Science; Contrast Media; Mice, Transgenic; Adenocarcinoma; Clofazimine; Sensitivity and Specificity; Photoacoustic Techniques; Mice; 03 medical and health sciences; Chlorides; Animals; Q; R; Prostate; Prostatic Neoplasms; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Nanomedicine; Microscopy, Fluorescence; Medicine; Nanoparticles; Research Article

Prostate cancer was the most common form and had the second highest death rate of male cancer in the United States in 2015. Current diagnosis techniques, such as prostate-specific antigen tests, transrectal ultrasound scans, and biopsies, are often inconclusive, and in the latter case, invasive. Here, we explore the use of clofazimine hydrochloride nanoparticles (CFZ-HCl NPs), a repurposed formulation from an FDA-approved antimycobacterial agent, as a photoacoustic contrast agent for the evaluation of prostate cancer due to its macrophage-targeting capabilities and high optical absorbance at 495 nm. Using a transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model, our results indicate a preferential accumulation of intravenously injected CFZ-HCl NPs in cancerous prostates over normal prostates. Differences in accumulation of CFZ-HCl NPs between cancerous and normal prostates were determined using a two-wavelength unmixing technique via ex vivo photoacoustic imaging. Thus, intravenous injection of CFZ-HCl NPs leads to differences in the interactions of the particles with cancerous vs normal prostates, while allowing for photoacoustic detection and analysis of prostate cancer. These findings could lead to the development of a new noninvasive technique for the detection and monitoring of prostate cancer progression in an animal model that can potentially be translated to human patients.