Harnessing platinum(IV) prodrugs as versatile photoinitiators and photocrosslinkers for multifunctional hydrogels and protein labeling

Jiaqian Xu, Qiyuan Zhou, Guohan Sun, Gongyuan Liu, Shu Chen, Zhao Yue, Ka-Yan Ng, Houzong Yao, Fu Shing Li, Yung-Kang Peng and Guangyu Zhu ()
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Jiaqian Xu: City University of Hong Kong
Qiyuan Zhou: City University of Hong Kong
Guohan Sun: City University of Hong Kong
Gongyuan Liu: City University of Hong Kong
Shu Chen: City University of Hong Kong
Zhao Yue: City University of Hong Kong
Ka-Yan Ng: City University of Hong Kong
Houzong Yao: City University of Hong Kong
Fu Shing Li: City University of Hong Kong
Yung-Kang Peng: City University of Hong Kong
Guangyu Zhu: City University of Hong Kong

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Photoresponsive molecules have revolutionized the fields of chemistry, biology, and medicine by enabling precise spatiotemporal control through external light stimuli. While extensive efforts have been employed to investigate the photochemical properties of Pt(IV) coordination complexes, their biomedical applications are still limited to chemotherapeutic functions. Herein, the photochemistry of clinical drug-based Pt(IV) prodrugs is investigated. Surprisingly, Pt(IV) complexes, rather than their Pt(II) counterparts, exhibit rapid photolysis upon irradiation at 365 nm, generating various reactive species including ROS and platinum radicals. Exploiting these unique photolysis products, we demonstrate alternative uses of Pt(IV) prodrugs as photoinitiators, enabling facile fabrication of multifunctional macromolecular materials such as antibacterial and conductive hydrogels for motion sensing. Efficient protein crosslinking further suggests that Pt(IV) coordination complexes can be employed as photocrosslinkers for gelatin hydrogelation and as reagents for protein photoreactive labeling. This comprehensive investigation significantly broadens the biomedical applications of Pt(IV) complexes beyond anticancer prodrugs, expanding the current repertoire of phototriggered biomedical applications using metal complexes. Our findings offer an avenue to harness the untapped potential of Pt(IV) prodrugs, paving the way for the development of advanced photoresponsive systems with diverse biomedical and material applications.

Date: 2025
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DOI: 10.1038/s41467-025-63958-2

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