Indocyanine green assembled free oxygen-nanobubbles towards enhanced near-infrared induced photodynamic therapy

Photodynamic therapy (PDT) has shown a promising capability for cancer treatment with minimal side effects. Indocyanine green (ICG), the only clinically approved near-infrared (NIR) fluorophore, has been used as a photosensitizer for PDT in clinical application. However, the main obstacle of directly utilizing ICG in the clinic lies in its low singlet oxygen (¹O₂) quantum yield (QY) and instability in aqueous solution. To improve the PDT efficacy of ICG, free ICG molecules were assembled with free oxygen nanobubbles (NBs-O₂) to fabricate ICG-NBs-O₂ by hydrophilic–hydrophobe interactions on the gas–liquid interface. Interestingly, ¹O₂ QY of ICG-NBs-O₂ solution was significantly increased to 1.6%, which was estimated to be 8 times as high as that of free ICG solution. Meanwhile, ICG-NBs-O₂ exhibited better aqueous solution stability compared with free ICG. Furthermore, through establishing tumor models in nude mice, the therapeutic efficacy of ICG-NBs-O₂ was also assessed in the PDT treatment of oral cancer. The tumor volume in ICG-NBs-O₂ treated group on day 14 decreased to 0.56 of the initial tumor size on day 1, while the tumor volume in free ICG treated group increased to 2.4 times. The results demonstrated that ICG-NBs-O₂ showed excellent tumor ablation in vivo. Therefore, this facile method provided an effective strategy for enhanced PDT treatment of ICG and showed great potential in clinical application.