Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China; School of Pharmacy, Binzhou Medical University, Yantai 264003, China.
Key Laboratory of Structure-Based Drug Design, Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
J Control Release. 2018 Jun 10;279:234-242. doi: 10.1016/j.jconrel.2018.04.038. Epub 2018 Apr 19.
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 dye–MAOA 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.
前列腺癌（PCa）是美国男性中最常见的恶性肿瘤，导致发病率和死亡率都很高，而现有的治疗方法对激素难治性前列腺癌（HRPC）和转移性前列腺癌患者的治疗效果有限。最近的研究表明，晚期前列腺癌表现出单胺氧化酶 A（MAOA）表达增加，MAOA 是一种线粒体酶，MAOA 活性抑制可限制转移并延长前列腺癌异种移植小鼠的存活时间。这些发现表明 MAOA 可以成为治疗前列腺癌的潜在靶点。基于此，我们鉴定并合成了一种近红外荧光（NIRF）七甲川染料-MAOA 抑制剂偶联物（NIR-INH），用于同时进行前列腺癌成像、靶向和治疗。该偶联物将靶向线粒体的 NIRF 染料与 MAOA 抑制剂异烟肼（INH）结合在一起。NIR-INH 在前列腺癌异种移植中表现出特异性靶向，并显著抑制肿瘤生长。此外，NIR-INH 治疗没有明显的毒性，这是其相对于传统化疗的显著优势。这些结果表明，NIR-INH 具有前列腺癌靶向、成像和高效抗癌作用，提示其是一种有潜力的、基于影像的抗肿瘤策略。
