Organogold(III) Complexes Display Conditional Photoactivities: Evolving From Photodynamic into Photoactivated Chemotherapy in Response to O2 Consumption for Robust Cancer Therapy

Photodynamic therapy (PDT) is a spatiotemporally controllable, powerful approach in combating cancers but suffers from low activity under hypoxia, whereas photoactivated chemotherapy (PACT) operates in an O2‐independent manner but compromises the ability to harness O2 for potent photosensitization. Herein we report that cyclometalated gold(III)‐alkyne complexes display a PDT‐to‐PACT evolving photoactivity for efficient cancer treatment. On the one hand, the gold(III) complexes can act as dual photosensitizers and substrates, leading to conditional PDT activity in oxygenated condition that progresses to highly efficient PACT (ϕ up to 0.63) when O2 is depleted in solution and under cellular environment. On the other hand, the conditional PDT‐to‐PACT reactivity can be triggered by external photosensitizers in a similar manner in vitro and in vivo, giving additional tumor‐selectivity and/or deep tissue penetration by red‐light irradiation that leads to robust anticancer efficacy. Oxygen‐dependent photo‐reactivity for robust tumor therapy: A PDT‐to‐PACT evolving photo‐reactivity with response to oxygen‐consumption was found in cyclometalated gold(III)‐alkyne complexes, leading to potent cytotoxicity towards cancer cells, strong anti‐angiogenesis in zebrafish, and efficient suppression of mouse tumor xenografts.