Mitochondria-targeted prostate cancer therapy using a near-infrared fluorescence dye-monoamine oxidase A inhibitor conjugate.

ABSTRACT

Prostate cancer (PCa) is the most frequent malignant cancer among men in the USA, leading to substantial morbidity and mortality, while the existing treatments have restricted therapeutic benefits for patients with hormone-refractory PCa (HRPC) and metastatic PCa. Recent studies show that advanced PCa exhibits an increase in the expression of monoamine oxidase A (MAOA) which is a mitochondria enzyme, and MAOA activity inhibition could restrict metastasis and extend mice survival in PCa xenografts. These findings suggest MAOA can be a potential target to treat PCa. For this reason, we identify and synthesize a near-infrared fluorescence (NIRF) heptamethine dye­MAOA inhibitor conjugate (NIR-INH) for simultaneous PCa imaging, targeting and therapy. The conjugate combines a NIRF dye for mitochondria targeting with the MAOA inhibitor isoniazid (INH). NIR-INH exhibits specific targeting in PCa xenografts and markedly inhibited tumor growth. Furthermore, there is no obvious toxicity with NIR-INH treatment, which is a remarkable superiority towards traditional chemotherapy. These results indicate that NIR-INH has PCa targeting, imaging and high anticancer effectiveness, suggesting it is a potentially valuable image-guided anti-tumor strategy.