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Near-infrared-activated anticancer platinum(IV) complexes directly photooxidize biomolecules in an oxygen-independent manner


Conventional light-driven cancer therapeutics require oxygen and visible light to indirectly damage biomolecules, limiting their efficacy in deep, hypoxic tumours. Here we report the use of near-infrared-activated small-molecule Pt(IV) photooxidants to directly oxidize intracellular biomolecules in an oxygen-independent manner, achieving controllable and effective elimination of cancer stem cells. These Pt(IV) complexes accumulate in the endoplasmic reticulum and show low toxicity in the dark. Upon irradiation, the resultant metal-enhanced photooxidation effect causes them to robustly photooxidize survival-related biomolecules, induce intense oxidative stress, disrupt intracellular pH (pHi) homeostasis and initiate nonclassical necrosis. In vivo experiments confirm that the lead photooxidant can effectively inhibit tumour growth, suppress metastasis and activate the immune system. Our study validates the concept of metal-enhanced photooxidation and the subsequent chemotherapeutic applications, supporting the development of such localized photooxidants to directly damage intracellular biomolecules and decrease pHi as a strategy for effective metal-based drugs.

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Fig. 1: Photoactivation and electrochemistry properties of 5a and 5b.
Fig. 2: Photooxidants 5a and 5b effectively oxidized conventional intracellular biomolecules upon NIR light activation.
Fig. 3: Photooxidants 5a and 5b accumulated in the ER and effectively eliminated cancer cells upon NIR-light activation.
Fig. 4: Photooxidant 5a induces nonclassical necrosis after photoactivation.
Fig. 5: In vivo antitumour effects of 5a.

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Data availability

All relevant data supporting the findings of this study are available within the article and its supplementary information. Source data are provided with this paper.


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We thank the Hong Kong Research Grants Council (grants CityU 11307419, 11304318, 11303320 and 11302221, awarded to G.Z., and 11104020 awarded to M.-L.H.), the National Natural Science Foundation of China (grants 21877092 and 22077108, awarded to G.Z.) and the Science Technology and Innovation Committee of Shenzhen Municipality (JCYJ20210324120004011 to G.Z.; JCYJ20180507181627057 to M.-L.H.) for funding support. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Author information

Authors and Affiliations



Z.D. and G.Z. designed the study. Z.D. and G.Z. designed the Pt(IV) photooxidants. Z.D. and S.C. synthesized the complexes. Z.D., S.C., G.L., W.O., D. Liu., Y.Y.L., J.L., D. Lei. and G.Z. characterized the chemical and physical properties of these complexes and analysed the data. Z.D. performed in vitro experiments. Z.D. and H.L. carried out the western blotting experiments. Z.D., H.L., M.H. and G.Z. analysed the data. Z.D., H.L. and X.W. carried out the PBMC co-culture experiments. Z.D. and F.X. carried out the hypoxia experiments. P.-C.L. and G.Z. directed the hypoxia experiments. Z.D., H.L., N.W., X.W., M.Y., M.H. and G.Z. performed the in vivo experiments and analysed the data. Z.D. and G.Z. wrote the paper. All authors edited and approved the final paper.

Corresponding authors

Correspondence to Ming-Liang He or Guangyu Zhu.

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Competing interests

G.Z. and Z.D. are inventors on US patent application no. 17/824,174 and Chinese patent application no. 202210706159.X submitted by the City University of Hong Kong, which covers the design, synthesis and application of the Pt(IV) photooxidants. Both patent applications have been published. The other authors declare no competing interests.

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Deng, Z., Li, H., Chen, S. et al. Near-infrared-activated anticancer platinum(IV) complexes directly photooxidize biomolecules in an oxygen-independent manner. Nat. Chem. 15, 930–939 (2023).

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