Rational design of an oxygen-enriching nanoemulsion for enhanced near-infrared laser activatable photodynamic therapy against hypoxic tumors

Photodynamic therapy (PDT) has emerged as one of the most promising modalities to treat cancers. However, the hypoxic microenvironment in tumors severely limits the efficiency of PDT. IR780 is a near-infrared light activatable photosensitizer for PDT. It has attracted intensive attention owing to its intriguing properties such as mitochondria-targeting ability and fluorescence imaging capability. Nevertheless, its application in tumor treatment is hampered by its low aqueous solubility and poor stability. To address these obstacles, here we designed a novel hierarchical nanoplatform containing a uniquely stable high loading capacity oxygen carrier (perfluoropolyether, in short, PFPE) and IR780. This nanoplatform (IR780-P/VV NE, in abbreviation for IR780-PFPE-in-water nanoemulsion) has no detectable dark cytotoxicity. It not only improves the aqueous solubility and stability of IR780, but also transports oxygen to relieve hypoxia and boosts the efficiency of near-infrared light triggered PDT via augmentation of reactive oxygen species generation. Particularly, the innovative nano-sized oxygen carrier developed in this research, P/W NE, is a potential universal platform for loading hydrophobic photosensitizers (including but not limited to IR780), sonosensitizers, or radiosensitizers, and simultaneously improving the therapeutic efficacy. Our results highlight the intriguing potential of the developed nanoemulsions for mitigating tumor hypoxia and enhancing the efficiencies of oxygen-dependent therapies including PDT, sonodynamic therapy, radiotherapy, and so on.