State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, People's Republic of China.
Department of Chemistry, Korea University, Seoul 02841, Korea.
J Am Chem Soc. 2022 Jan 12;144(1):163-173. doi: 10.1021/jacs.1c07372. Epub 2021 Dec 28.
The transformational effect of photoredox catalytic chemistries has inspired new opportunities, enabling us to interrogate nature in ways that are not possible otherwise and to unveil new biotechnologies in therapy and diagnosis. However, the deployment of artificial photoredox catalysis in living systems remains challenging, mired by the off-target risk and safety concerns of photocatalyst toxicity. Here, we present an appealing approach, namely conditionally activatable photoredox catalysis (ConAPC), and as a proof of concept design the first ConAPC architecture () based upon classic self-immolative chemistry, in which the inherent photocatalytic properties can be temporarily caged while the species becomes active only at the tumor sites via sensing to specific biomarkers. Such a masking strategy allows a spatial-temporal control of photoresponsivity and . In particular, for ConAPC design, a new biologically benign metal-free photocatalyst (), which is able to initiate NIR photoredox catalysis to manipulate the cellular electron pool in an O-independent mechanism of action, is identified. With this unique strategy, potent tumor-specific targeting photocatalytic eradication (TGI: 95%) is obtained in a mouse model. Impressively, favorable features such as high-resolution tumor recognition (SBR: 33.6) and excellent biocompatibility and safety are also achieved. This work therefore offers a new possibility for chemists to leverage artificial photocatalytic reactions toward the development of facile and intelligent photocatalytic theranostics.
光氧化还原催化化学的变革性影响激发了新的机遇，使我们能够以前所未有的方式探究自然，并揭示治疗和诊断中的新生物技术。然而，将人工光氧化还原催化应用于活系统仍然具有挑战性，其面临着非靶向风险和光催化剂毒性的安全问题。在这里，我们提出了一种有吸引力的方法，即条件激活光氧化还原催化（ConAPC），并作为概念验证设计，提出了第一个基于经典自耗竭化学的 ConAPC 架构（），其中固有光催化性质可以暂时被笼封，而该物质仅通过感应特定生物标志物在肿瘤部位变得活跃。这种掩蔽策略允许对光响应性进行时空控制。特别是，对于 ConAPC 设计，我们鉴定了一种新的生物相容性的无金属光催化剂（），它能够引发近红外光氧化还原催化，以在非 O 依赖性作用机制中操纵细胞电子库。采用这种独特的策略，在小鼠模型中实现了有效的肿瘤特异性靶向光催化消除（TGI：95%）。令人印象深刻的是，还实现了高分辨率肿瘤识别（SBR：33.6）、良好的生物相容性和安全性等优异性能。因此，这项工作为化学家们提供了一种新的可能性，使他们能够利用人工光催化反应来开发简便和智能的光催化治疗方法。
