Hypoxia in aggressively proliferating tumor cells has been demonstrated to restrict the efficiency of photodynamic therapy owing to its oxygen (O2 )-dependent generation of singlet oxygen (1 O2 ) from photosensitizers under light irradiation. To address this problem, we propose a small-molecule dye-based 1 O2 capturing agent, B1. B1 not only bears a near-infrared absorbing azo-boron dipyrromethene backbone, but also has 1,4-dimethylnaphthalene, which facilitates the capture of 1 O2 to form endoperoxide (B1-SO). B1-SO undergoes a reversible reaction via near-infrared photothermal stimulation, thus allowing 1 O2 release. Based on this mechanism, stable B1-SO containing micelles (B1-SO NPs) were prepared and employed as 1 O2 nanocarriers to ablate cancer cells in vitro. Taking advantage of this O2 -independent 1 O2 releasing ability, B1-SO NPs were demonstrated to have efficient cytotoxicity under near-infrared irradiation, especially in a hypoxic environment. The unique O2 -independent 1 O2 generation process of B1-SO NPs suggests they can be used as novel cancer phototherapy agents.
Keywords: cancer; hypoxia; nanoparticles; phototherapy; singlet oxygen carriers.
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