TY - JOUR
T1 - Fluorescein-Functionalized Iridium(III) Complexes as Dual-Mode Type I Photosensitizers for Hypoxia-Tolerant Photodynamic and X-ray-Induced Therapy
AU - Liu, Ji Qiang
AU - Tse, Anfernee Kai Wing
AU - Koncošová, Martina
AU - Ruml, Tomáš
AU - Tse, Yu Chung
AU - Liu, Chuang Jun
AU - Zelenka, Jaroslav
AU - Kirakci, Kaplan
AU - Lang, Kamil
AU - Lee, Chi Sing
AU - Wong, Keith Man Chung
N1 - The presented research was financially supported by the National Natural Science Foundation of China (Grant Nos. 81671758 and 31571013), the Guangdong Natural Science Foundation of Research Team (2016A030312006), and the Shenzhen Science and Technology Program (Grant Nos. JCYJ20160429191503002, JCYJ20170818162522440 and JCYJ20170818154843625). K.M.-C.W. acknowledges the National Natural Science Foundation of China (Grant No. 21771099) and the Science, Technology and Innovation Commission of Shenzhen Municipality (Grant Nos. JCYJ20170817110721105 and JCYJ20190809165411528).
Publisher Copyright:
© 2025 American Chemical Society.
PY - 2025/6/9
Y1 - 2025/6/9
N2 - The development of photosensitizers that function effectively in hypoxic environments and enable deep-tissue treatment remains a significant challenge in photodynamic therapy (PDT). Here, we report two novel Ir(III) complexes functionalized with fluorescein designed as efficient Type I photosensitizers for both light-driven PDT and X-ray-induced PDT (X-PDT). By populating the triplet state of the fluorescein ligands, these complexes facilitate the generation of reactive oxygen species (ROS) through electron transfer, producing superoxide anion radicals (O2•-) and hydroxyl radicals (•OH) under irradiation. The complexes exhibit pronounced phototoxicity against cancer cells, particularly under hypoxic conditions, where oxygen-dependent Type II photosensitizers are less effective. Remarkably, these complexes also demonstrate direct X-ray activation, offering a solution for deep-tissue cancer treatment. The lead complex, PS1, outperforms existing systems by efficiently generating both singlet oxygen O2(1Δg) and free radicals, enabling synergistic Type I and II PDT effects. This work represents a major advancement in the design of oxygen-independent PDT agents by using fluorescein’s triplet state, with potential applications in deep-tissue and hypoxic tumor environments.
AB - The development of photosensitizers that function effectively in hypoxic environments and enable deep-tissue treatment remains a significant challenge in photodynamic therapy (PDT). Here, we report two novel Ir(III) complexes functionalized with fluorescein designed as efficient Type I photosensitizers for both light-driven PDT and X-ray-induced PDT (X-PDT). By populating the triplet state of the fluorescein ligands, these complexes facilitate the generation of reactive oxygen species (ROS) through electron transfer, producing superoxide anion radicals (O2•-) and hydroxyl radicals (•OH) under irradiation. The complexes exhibit pronounced phototoxicity against cancer cells, particularly under hypoxic conditions, where oxygen-dependent Type II photosensitizers are less effective. Remarkably, these complexes also demonstrate direct X-ray activation, offering a solution for deep-tissue cancer treatment. The lead complex, PS1, outperforms existing systems by efficiently generating both singlet oxygen O2(1Δg) and free radicals, enabling synergistic Type I and II PDT effects. This work represents a major advancement in the design of oxygen-independent PDT agents by using fluorescein’s triplet state, with potential applications in deep-tissue and hypoxic tumor environments.
UR - http://www.scopus.com/inward/record.url?scp=105006789094&partnerID=8YFLogxK
U2 - 10.1021/acs.inorgchem.5c00894
DO - 10.1021/acs.inorgchem.5c00894
M3 - Journal article
AN - SCOPUS:105006789094
SN - 0020-1669
VL - 64
SP - 10894
EP - 10905
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 22
ER -
