Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 45, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202212689
Keywords
Anticancer Metallodrug; Gold Medicine; Metal Prodrug; Photoactivated Chemotherapy; Photodynamic Therapy
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Funding
- National Natural Science Foundation of China [22122706]
- Guangdong Science and Technology Department [2019QN01C125]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515012347, 2020A1515110508]
- Guangzhou Science and Technology Projects [202102020790]
- Guangdong Provincial Key Lab of Chiral Molecule and Drug Discovery [2019B030301005]
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This study reports a novel approach combining photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) for cancer treatment. Cyclometalated gold(III)-alkyne complexes can achieve conditional PDT and highly efficient PACT under oxygenated and hypoxic conditions respectively, and the conditional PDT-to-PACT reactivity can be triggered by external photosensitizers, providing tumor selectivity and deep tissue penetration.
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 O-2-independent manner but compromises the ability to harness O-2 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 (phi up to 0.63) when O-2 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.
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