School of Pharmaceutical Science (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 518107, P. R. China.
School of Bioscience and Biopharmaceutics, Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou, 510006, P. R. China.
Angew Chem Int Ed Engl. 2022 Jun 7;61(23):e202202098. doi: 10.1002/anie.202202098. Epub 2022 Apr 6.
Quantifying the content of metal-based anticancer drugs within single cancer cells remains a challenge. Here, we used single-cell inductively coupled plasma mass spectrometry to study the uptake and retention of mononuclear (Ir1) and dinuclear (Ir2) Ir photoredox catalysts. This method allowed rapid and precise quantification of the drug in individual cancer cells. Importantly, Ir2 showed a significant synergism but not an additive effect for NAD(P)H photocatalytic oxidation. The lysosome-targeting Ir2 showed low dark toxicity in vitro and in vivo. Ir2 exhibited high photocatalytic therapeutic efficiency at 525 nm with an excellent photo-index in vitro and in tumor-bearing mice model. Interestingly, the photocatalytic anticancer profile of the dinuclear Ir2 was much better than the mononuclear Ir1, indicating for the first time that dinuclear metal-based photocatalysts can be applied for photocatalytic anticancer treatment.
定量测定单个癌细胞内基于金属的抗癌药物含量仍然是一个挑战。在这里，我们使用单细胞电感耦合等离子体质谱法研究单核（Ir1）和双核（Ir2）Ir 光氧化还原催化剂的摄取和保留。该方法允许快速准确地定量测定单个癌细胞中的药物。重要的是，Ir2 对 NAD(P)H 光催化氧化表现出显著的协同作用，但没有相加作用。溶酶体靶向 Ir2 在体外和体内显示出低的暗毒性。Ir2 在 525nm 处表现出高的光催化治疗效率，具有优异的体外光指数和荷瘤小鼠模型中的光指数。有趣的是，双核 Ir2 的光催化抗癌谱明显优于单核 Ir1，这首次表明双核金属基光催化剂可用于光催化抗癌治疗。
