A Mitochondrion‐Localized Two‐Photon Photosensitizer Generating Carbon Radicals Against Hypoxic Tumors

Abstract

The efficacy of photodynamic therapyi st ypically 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 am itochondrion-localized carbon-radical initiator.I ts emission is turned on under hypoxic conditions after reduction by reductase.F urthermore,i ts two-photon excitation properties (l ex = 730 nm) are highly desirable for imaging.U pon irradiation, the reduced form of the complex generates carbon radicals,l eading to al oss of mitochondrial membrane potential and cell death (IC 50 light = 2.1 mm,IC 50 dark = 58.2 mm,P I= 27.7). The efficacy of the complex as aP DT agent was also demonstrated under hypoxic conditions in vivo. To the best of our knowledge,i ti st he first metal-complexbased theranostic agent which can generate carbon radicals for oxygen-independent two-photon photodynamic therapy.

Phosphorescent Iridium(III) Complexes for Anticancer Applications

“…Chao, Zhang, and Chen reported a mitochondrion-localized two-photon photosensitizer generating carbon radicals against hypoxic tumors (34, Figure 12). [47] The emission of 34 is turnedon under hypoxic conditions after reduction by reductase and…”

“…Reproduced from ref. [47] available for bioimaging. Upon irradiation, the reduced form of 34 (34-red) generates carbon radicals leading to the loss of mitochondrial membrane potential and cell death.…”

A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy

“…However, one of the bottlenecks of PDT is the low tissue penetration depth of light. To enhance PDT efficiency, near-infrared two-photon and three-photon excitation have been employed, to increase the penetration depth of excitation light 14 , 15 . Nevertheless, the multi-photon light source is rather costly and troublesome in moving, thus it is not suitable for in vivo or clinical experiments 16 , 17 .…”

Boosting cancer therapy efficiency via photoinduced radical production

“…However, the produced toxic species are related to oxygen, indicating that the photodynamic therapeutic efficiency of these photosensitizers still relies on oxygen concentration although they require much lower oxygen concentration than traditional photosensitizers. 27 To well defeat hypoxia tumors, it would be a promising manner to develop an entirely oxygen-independent platform with remote controllable ability.…”