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(Ce6-PEG-Pt(IV) conjugate) in upconverting nanoparticles that exhibit dramatically enhanced photocytotoxicity in hypoxic tumour models with NIR (980nm) irradiation.7 Diazido Pt(IV) complexes themselves show potential for a novel form of photoactivated chemotherapy (PACT). They are highly stable in the dark but decompose upon irradiation with visible light to release cytotoxic azidyl radicals and reactive oxygen species, as well as DNA-binding Pt(II) species.8 Axial derivatisation of diazido Pt(IV) complexes with anticancer drugs or cancer-targeting vectors can improve the photo-selectivity of the agents and red-shift their activation wavelength. Cancer-targeting proteins can assist the delivery of photosensi- tisers to tumours and increase selectivity versus normal tissue. For example, Rutherrin, a conjugate of TLD-1433 and apo-transferrin, exhibits enhanced cancer-targeting and photocytotoxicity.3 Due to the abnormal mitochondrial function of cancer cells, mitochondrial-targeting can also lead to improved cancer selectivity. Triphenylphosphonium (TPP) and dichloroacetate (DCA) have been conjugated to photosensitisers as mitochondrial-targeting tags. TPP and a Ru(II) photosensitiser bound to human serum albumin (HSA) as a nanocarrier to form cHSA-PEO-TPP-Ru, exhibits mitochondrial localisation, enhanced 1O generation, cancer accumulation and photocytotoxicity.9 Finally, PDT can not treat advanced disseminated disease due to the difficulty of light delivery and the limited penetration depth. Photothermal therapy (PTT) is a new treatment for advanced tumours, in which photosensitisers absorb NIR and release vibrational energy (heat) to kill cancer cells, independent of oxygen.10 However, the composition of current PTT photosensi- tisers, mainly inorganic nanomaterials, needs to be optimised if they are to become clinical drugs. The introduction of light into cancer treatment can provide precise tumour localisation of treatment and low invasiveness. Due to the novel mechanism of action, phototherapy is not usually cross-resistant with other cancer treatments, and thus can be a component of combination treatments. Current new develop- ments in the design of both light sources and photoactive agents suggest that oncological phototherapy will have wider applica- tions in the future. AUTHOR CONTRIBUTIONS All authors contributed to the writing, revision and approval of this manuscript. ADDITIONAL INFORMATION Ethics approval and consent to participate Not applicable. Consent to publish Not applicable. Data availability Not applicable. 2 How promising is phototherapy for cancer? H Shi and PJ Sadler Competing interests The authors declare no competing interests. Funding information This work was supported by Innovate UK for their funding through the ICURe programme. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. REFERENCES 1. van Straten, D., Mashayekhi, V., de Bruijn, H., Oliveira, S. & Robinson, D. Oncologic photodynamic therapy: basic principles, current clinical status and future direc- tions. Cancers 9, 19 (2017). 2. Imberti, C., Zhang, P., Huang, H. & Sadler, P. J. New designs for phototherapeutic transition metal complexes. Angew. Chem. Int. Ed. 59, 61–73 (2020). 3. Monro, S., Colón, K. L., Yin, H., Roque, J., Konda, P., Gujar, S., Thummel, R. P., Lilge, L., Cameron, C. G. & McFarland, S. A. Transition metal complexes and photodynamic therapy from a tumor-centered approach: challenges, opportunities, and highlights from the development of TLD1433. Chem. Rev. 119, 797–828 (2019). 4. Brancaleon, L. & Moseley, H. Laser and non-laser light sources for photodynamic therapy. Lasers Med. Sci. 17, 173–186 (2002). 5. Morton, C. A. & Braathen, L. R. Daylight photodynamic therapy for actinic kera- toses. Am. J. Clin. Dermatol. 19, 647–656 (2018). 6. Huang, H., Banerjee, S., Qiu, K., Zhang, P., Blacque, O., Malcomson, T., Paterson, M. J., Clarkson, G. J., Staniforth, M., Stavros, V. G., Gasser, G., Chao, H. & Sadler, P. J. Targeted photoredox catalysis in cancer cells. Nat. Chem. 11, 1041–1048 (2019). 7. Xu, S., Zhu, X., Zhang, C., Huang, W., Zhou, Y. & Yan, D. Oxygen and Pt(II) self- generating conjugate for synergistic photo-chemo therapy of hypoxic tumor. Nat. Commun. 9, 2053 (2018). 8. Shi, H., Imberti, C. & Sadler, P. J. Diazido platinum(IV) complexes for photo- activated anticancer chemotherapy. Inorg. Chem. Front. 6, 1623–1638 (2019). 9. Chakrabortty, S., Agrawalla, B. K., Stumper, A., Veg, N. M., Fischer, S., Reichardt, C., Koegler, M., Dietzek, B., Feuring-Buske, M., Buske, C., Rau, S. & Weil, T. Mito- chondria targeted protein-ruthenium photosensitizer for efficient photodynamic applications. J. Am. Chem. Soc. 139, 2512–2519 (2017). 10. Zou, L., Wang, H., He, B., Zeng, L., Tan, T., Cao, H., He, X., Zhang, Z., Guo, S. & Li, Y. Current approaches of photothermal therapy in treating cancer metastasis with nanotherapeutics. Theranostics 6, 762–772 (2016). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. © The Author(s) 2020 873PDF Image | How promising is phototherapy for cancer
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