Development of an Azo-Based Photosensitizer Activated under Mild Hypoxia for Photodynamic Therapy

Abstract

Photodynamic therapy (PDT) utilizes photoirradiation in the presence of photosensitizers to ablate cancer cells via generation of singlet oxygen (O), but it is important to minimize concomitant injury to normal tissues. One approach for achieving this is to use activatable photosensitizers that can generate O only under specific conditions. Here, we report a novel photosensitizer that is selectively activated under hypoxia, a common condition in solid tumors. We found that introducing an azo moiety into the conjugated system of a seleno-rosamine dye effectively hinders the intersystem crossing process that leads to O generation. We show that the azo group is reductively cleaved in cells under hypoxia, enabling production of O to occur. In PDT in vitro, cells under mild hypoxia, within the range typically found in solid tumors (up to about 5% O), were selectively ablated, leaving adjacent normoxic cells intact. This simple and practical azo-based strategy should be widely applicable to design a range of activatable photosensitizers.

Hybrid Rhodamine Fluorophores in the Visible/NIR Region for Biological Imaging

“…[50] Recently,Hanaokasgroup also employed 87 to design aSerhodamine-based hypoxia-sensitive fluorescence probe.T his was achieved by introducing an azo moiety into the conjugated system of rhodamine fluorophores. [51] When Naganos group studied Si-rhodamine fluorophores,t hey also investigated Ge-substituted rhodamine dyes 88 (l em = 649 nm) and Te -substituted rhodamine dyes 89-90.F luorophore 89 has al ow quantum yield (< 0.001) but can be oxidized to fluorescent Te O-rhodamines 90 (l em = 686 nm) with ah igher quantum yield of 0.18. This renders Te -substituted rhodamine dyes 89 suitable as reversible NIR probes for reactive oxygen species (ROS).…”

Boron Dipyrromethene Nano‐Photosensitizers for Anticancer Phototherapies

“…Compared with PDT, PTT has emerged as a potentially safe option because the off‐target sensitizing effects and irreversible oxidative damage by ROS are frequently observed during PDT . Furthermore, most PDT agents are oxygen dependent and are ineffective in tumors with hypoxic environments .…”

A Bacteriochlorin‐Based Metal–Organic Framework Nanosheet Superoxide Radical Generator for Photoacoustic Imaging‐Guided Highly Efficient Photodynamic Therapy

“…[1][2][3] Photodynamic therapy (PDT) utilizes a photosensitizer (PS) excited by an appropriate light irradiation to generate reactive oxygen species (ROS); in most of cases, it involves a process that the ground triplet-state molecular oxygen ( 3 O 2 ) is transformed to the reactive singlet oxygen ( 1 O 2 ) via the type II mechanism extremely dependent on the concentration of oxygen (O 2 ). [1][2][3] Photodynamic therapy (PDT) utilizes a photosensitizer (PS) excited by an appropriate light irradiation to generate reactive oxygen species (ROS); in most of cases, it involves a process that the ground triplet-state molecular oxygen ( 3 O 2 ) is transformed to the reactive singlet oxygen ( 1 O 2 ) via the type II mechanism extremely dependent on the concentration of oxygen (O 2 ).…”