Photothermal Responsive Singlet Oxygen Nanocarriers for Hypoxic Cancer Cell Ablation

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.