Department of Chemistry, Korea University, Seoul 02841, Korea.
Department of Life Sciences, Korea University, Seoul 02841, Korea.
ACS Appl Bio Mater. 2021 Mar 15;4(3):2120-2127. doi: 10.1021/acsabm.0c01322. Epub 2020 Nov 24.
Melanoma is the most threatening form of metastatic skin cancer that develops from melanocytes and causes a large majority of deaths due to poor therapeutic prognosis. It has significant limitations in treatment because it shows great resistance to chemotherapy, radiotherapy, and other therapeutic methods. A noninvasive and clinically accepted therapeutic modality, photodynamic therapy (PDT), is a promising treatment option, but it is limitedly applied for melanoma skin cancer treatment. This is because most of the photosensitizers are unlikely to be expected to have a remarkable effect on melanoma due to drug efflux by melanin pigmentation and intrinsic antioxidant defense mechanisms. Moreover, melanin is a dominant absorber in the spectral region of 500-600 nm that can cause the decreased photoreaction efficiency of photosensitizers. Herein, to overcome these drawbacks, we have developed a phenylthiourea-conjugated BODIPY photosensitizer () for tyrosinase-positive melanoma-targeted PDT. In light of our results, it exhibited an enhanced cytotoxic efficacy compared to BDP, a parallel PDT agent that absence of phenylthiourea unit. shows outstanding effects of increased oxidative stress by an enhanced cellular uptake of the tyrosinase positive melanoma cell line (B16F10). This work presents increased therapeutic efficacy through the combined therapeutic approach, enabling enhanced reactive oxygen species (ROS) generation as well as overcoming the critical limitations of melanoma.
黑色素瘤是最具威胁性的转移性皮肤癌，由黑色素细胞发展而来，由于治疗预后不佳，导致大多数患者死亡。由于其对化疗、放疗和其他治疗方法具有很强的抵抗力，因此在治疗方面存在很大的局限性。光动力疗法（PDT）是一种非侵入性和临床可接受的治疗方式，是一种有前途的治疗选择，但由于黑色素的药物外排和内在抗氧化防御机制，大多数光敏剂不太可能对黑色素瘤产生显著效果，因此其应用有限。此外，黑色素是 500-600nm 光谱区域的主要吸收体，可导致光敏剂的光反应效率降低。有鉴于此，为了克服这些缺点，我们开发了一种与苯硫脲偶联的 BODIPY 光敏剂（），用于酪氨酸酶阳性黑色素瘤的靶向 PDT。根据我们的结果，与缺乏苯硫脲单元的平行 PDT 试剂 BDP 相比，表现出增强的细胞毒性作用。与缺乏苯硫脲单元的平行 PDT 试剂 BDP 相比，表现出增强的细胞毒性作用。显示出通过增强的细胞摄取对酪氨酸酶阳性黑色素瘤细胞系（B16F10）增加氧化应激的出色效果。这项工作通过联合治疗方法提高了治疗效果，能够增强活性氧（ROS）的产生，并克服了黑色素瘤的关键局限性。
