Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, School of Chemical Science and Technology, Yunnan University, No. 2 North Cuihu Road, Kunming, 650091, P. R. China.
First Affiliated Hospital of Kunming Medical University, Kunming, 650032, P. R. China.
Angew Chem Int Ed Engl. 2022 Sep 19;61(38):e202208721. doi: 10.1002/anie.202208721. Epub 2022 Aug 17.
A series of dinuclear Ru complexes with extremely high TPA cross sections in the range of 800-900 nm have been designed. The amphiphilic complex Ru3 containing tert-butyl groups has balanced performance in singlet oxygen generation and photothermal conversion and becomes the ideal drug candidate of the series. Ru3 targets mitochondria without penetrating the nucleus, which substantially increases its photodynamic therapy activity and reduces its dark cytotoxicity. Ru3 successfully suppresses melanoma tumor growth in vitro and in vivo with combined photodynamic and photothermal therapy under low light dose irradiation of an 808 nm low-power laser, avoiding the known PDT resistance in melanoma. The excellent therapeutic effect of Ru3 facilitates its applications in further human trials for larger or deeper buried tumors, thereby becoming a prospective candidate for a new generation of low-power IR-driven dual PDT/PTT drugs.
设计了一系列具有 800-900nm 范围内极高 TPA 截面的双核 Ru 配合物。含有叔丁基的两亲性配合物 Ru3 在单线态氧生成和光热转换方面具有平衡的性能，成为该系列的理想药物候选物。Ru3 靶向线粒体而不穿透细胞核，这大大提高了其光动力治疗活性，降低了其暗毒性。Ru3 在低功率 808nm 激光的低光剂量照射下，通过光动力和光热联合治疗，成功抑制了体外和体内黑色素瘤肿瘤的生长，避免了黑色素瘤已知的 PDT 耐药性。Ru3 的优异治疗效果使其能够进一步应用于更大或更深埋藏肿瘤的人体试验，从而成为新一代低功率 IR 驱动的双重 PDT/PTT 药物的有前途的候选物。
