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A Mitochondrion‐Localized Two‐Photon Photosensitizer Generating Carbon Radicals Against Hypoxic Tumors
Author(s) -
Kuang Shi,
Sun Lingli,
Zhang Xianrui,
Liao Xinxing,
Rees Thomas W.,
Zeng Leli,
Chen Yu,
Zhang Xiting,
Ji Liangnian,
Chao Hui
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202009888
Subject(s) - photodynamic therapy , radical , photosensitizer , chemistry , photochemistry , reactive oxygen species , oxygen , biophysics , two photon excitation microscopy , superoxide , mitochondrion , biochemistry , fluorescence , organic chemistry , biology , enzyme , physics , quantum mechanics
The efficacy of photodynamic therapy is typically reliant on the local concentration and diffusion of oxygen. Due to the hypoxic microenvironment found in solid tumors, oxygen‐independent photosensitizers are in great demand for cancer therapy. We herein report an iridium(III) anthraquinone complex as a mitochondrion‐localized carbon‐radical initiator. Its emission is turned on under hypoxic conditions after reduction by reductase. Furthermore, its two‐photon excitation properties ( λ ex =730 nm) are highly desirable for imaging. Upon irradiation, the reduced form of the complex generates carbon radicals, leading to a loss of mitochondrial membrane potential and cell death (IC 50 light =2.1 μ m , IC 50 dark =58.2 μ m , PI=27.7). The efficacy of the complex as a PDT agent was also demonstrated under hypoxic conditions in vivo. To the best of our knowledge, it is the first metal‐complex‐based theranostic agent which can generate carbon radicals for oxygen‐independent two‐photon photodynamic therapy.