Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2019 Jul 15;14(7):e0219655. doi: 10.1371/journal.pone.0219655. eCollection 2019.
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.
前列腺癌是 2015 年美国男性癌症中最常见的形式，死亡率排名第二。目前的诊断技术，如前列腺特异性抗原检测、经直肠超声扫描和活检，往往不够明确，而在后一种情况下，还具有侵入性。在这里，我们探索了使用盐酸氯法齐明纳米颗粒（CFZ-HCl NPs），一种来自 FDA 批准的抗分枝杆菌药物的重新利用制剂，作为光声对比剂来评估前列腺癌，因为它具有巨噬细胞靶向能力和在 495nm 处的高光吸收。使用转基因前列腺腺癌（TRAMP）小鼠模型，我们的结果表明，静脉注射的 CFZ-HCl NPs 优先积聚在癌变的前列腺中，而不是正常的前列腺中。通过离体光声成像的双波长解混技术确定 CFZ-HCl NPs 在癌变和正常前列腺中的积累差异。因此，CFZ-HCl NPs 的静脉注射导致了颗粒与癌变前列腺与正常前列腺之间相互作用的差异，同时允许对前列腺癌进行光声检测和分析。这些发现可能导致开发一种新的非侵入性技术，用于在动物模型中检测和监测前列腺癌的进展，该技术有可能转化为人类患者。
