Oxygen nanobubbles of ICG dimers achieve self-cascade photothermal and photodynamic therapy for hypoxia-reversible tumor treatment
Xiang Sun, Zheng Zhang, Moran Wang, Yuqin Chen, Xiang Meng, Wenjun Zhao, Juan Jin, Wentao Yang, Chengwan Xia, Yuxin Wang, Shengliang Li, Bin Huang, Ning Gu
Abstract
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 (O<sub>2</sub>-NBs), DICG/O<sub>2</sub>-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/O<sub>2</sub>-NBs can switch J-aggregates of DICG into DICG monomers with efficient O<sub>2</sub> gas liberation, while producing hydroxyl radicals for type I PDT. Additionally, the evolved DICG monomer reacts with the released O<sub>2</sub> to generate plenty of <sup>1</sup>O<sub>2</sub> 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>.