Two-Dimensional Nanosonosensitizers Facilitate Energy Transfer to Enhance Sonodynamic Therapy.

Although sonodynamic therapy (SDT) has shown promise for cancer treatment, the lack of efficient sonosensitizers (SSs) has limited the clinical application of SDT. Here we report a new strategy for designing efficient nanosonosensitizers based on two-dimensional nanoscale metal-organic layers (MOLs). Composed of Hf-oxo secondary building units (SBUs) and iridium-based linkers (DBB-Ir), the MOL was anchored with 5,10,15,20-tetra(p-benzoato)porphyrin (TBP) sensitizers on the SBUs to afford TBP@MOL. TBP@MOL showed 14.1- and 7.4-fold higher singlet oxygen ( 1 O 2 ) generation than free TBP ligands and Hf-TBP, a three-dimensional nanoscale metal-organic framework, respectively. The 1 O 2 generation of TBP@MOL is enhanced by isolating TBP SSs on the SBUs of the MOL, which prevents aggregation-induced quenching of the excited sensitizers, and by triplet-triplet Dexter energy transfer between excited DBB-Ir bridging ligands and TBP SSs, which more efficiently captures the broad-spectrum sonoluminescence. Anchoring TBP SSs on the MOL surface also enhances the energy transfer between the excited sensitizer and ground-state triplet oxygen to increase 1 O 2 generation efficacy. In mouse models of colorectal and breast cancer, TBP@MOL demonstrated significantly higher SDT efficacy than Hf-TBP and TBP. This work uncovers a new strategy to design effective nanosonosensitizers by facilitating energy transfer to efficiently capture broad-spectrum sonoluminescence and enhance 1 O 2 generation. This article is protected by copyright. All rights reserved.