Conditionally Activatable Photoredox Catalysis in Living Systems

Abstract

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 (Se-NO 2 ) 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 in vitro and in vivo. In particular, for ConAPC design, a new biologically benign metal-free photocatalyst (Se-NH 2 ), which is able to initiate NIR photoredox catalysis to manipulate the cellular electron pool in an O2-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.

Oxygen‐Tolerant Photoredox Catalysis Triggers Nitric Oxide Release for Antibacterial Applications

“…Having known that BNN‐NO 2 and BNN donors can be activated by fac ‐Ir(ppy) 3 photocatalyst under visible light irradiation with unique oxygen‐tolerant properties, we wondered whether this NO‐releasing platform could be operated in aqueous media. Note that photoredox catalysis in purely aqueous media would be quite beneficial for biomedical applications, which however remains a tough challenge due to the poor water‐solubility of many photocatalysts and the oxygen interferences [2] . To this end, we attempted to encapsulate hydrophobic fac ‐Ir(ppy) 3 photocatalyst into micellar nanoparticles consisting of BNN‐NO 2 /BNN moieties within the cores of micellar nanoparticles.…”

“…Note that photoredox catalysis in purely aqueous media would be quite beneficial for biomedical applications, which however remains a tough challenge due to the poor water-solubility of many photocatalysts and the oxygen interferences. [2] To this end, we attempted to encapsulate hydrophobic fac-Ir(ppy) 3 photocatalyst into micellar nanoparticles consisting of BNN-NO 2 / BNN moieties within the cores of micellar nanoparticles. BNN-NO 2 , BNN, and BNN-Me were then copolymerized with hexamethylene diisocyanate (HDI), followed by endcapping with poly(ethylene glycol) methyl ether (Scheme S2).…”

“…To this end, photoredox catalysis needs to be conducted in biological fluids, whereas many photocatalysts are incompatible with the complex physiological microenvironment. In addition, photoredox catalysis reactions are typically achieved by photo‐induced electron transfer and/or energy transfer mechanisms, in which the excited state of photocatalysts, especially for those operating in the triple state, can be significantly quenched by biologically relevant molecules such as oxygen [2] . Although prior removal of oxygen from reaction mixtures or the addition of oxygen‐scavenging agents is possible in chemical synthesis, it is difficult to remove oxygen in biological fluids without affecting the normal physiological microenvironment [3] .…”

“…In addition, photoredox catalysis reactions are typically achieved by photo-induced electron transfer and/or energy transfer mechanisms, in which the excited state of photocatalysts, especially for those operating in the triple state, can be significantly quenched by biologically relevant molecules such as oxygen. [2] Although prior removal of oxygen from reaction mixtures or the addition of oxygen-scavenging agents is possible in chemical synthesis, it is difficult to remove oxygen in biological fluids without affecting the normal physiological microenvironment. [3] Therefore, it remains challenging to develop oxygen-tolerant photoredox catalytic platforms that can be operated under physiological conditions.…”

BODIPY-Based Photothermal Agents for Cancer Treatment

“…Additional agents for phototherapy undergoing photoredox catalysis have been reported recently. [23,24] Furthermore, phototherapeutic treatment methods have emerged based on photothermal therapy (PTT). PTT applies functional biomedical and bioactive nanomaterials activated by light in the near-infrared (NIR) range to eliminate tumour cells via the generation of heat upon irradiation.…”