Oxygen nanobubbles of ICG dimers achieve self-cascade photothermal and photodynamic therapy for hypoxia-reversible tumor treatment

Simultaneous photothermal and photodynamic therapies (PTT and PDT) hold great promise for noninvasive tumor therapy. However, effective regulation of PTT and PDT with optimal synergistic effects remains a challenge. To date, there are only a few synergistic PTT and PDT methods with suitable collaborative effects due to the rarity of efficient nanoplatforms with good cascading properties. To overcome this limitation, a proof-of-concept of self-cascade PTT and PDT was developed for hypoxia-reversible tumor therapy. With the assembly of dimeric indocyanine green (DICG) with oxygen nanobubbles (O₂-NBs), DICG/O₂-NBs typically exhibit J-aggregates for significant PTT effects, with a high photothermal conversion efficiency of 51.45% under 880 nm light irradiation. Interestingly, the PTT performance of DICG/O₂-NBs can switch J-aggregates of DICG into DICG monomers with efficient O₂ gas liberation, while producing hydroxyl radicals for type I PDT. Additionally, the evolved DICG monomer reacts with the released O₂ to generate plenty of ¹O₂ for efficient type II PDT. With these advantages, the cascaded nanoplatform achieves good tumor targeting and biocompatibility, and thus has high tumor inhibition of 94.26%, with an obvious ability to reverse hypoxia. This work demonstrates the efficiency of self-cascade PTT and PDT nanomedicine for high-performance hypoxia-reversible tumor ablation, thus providing a new approach for the development of cascading phototheranostics <i>in vivo</i>.