Department of Chemistry, The University of Chicago, Chicago, IL, 60637, USA.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, China.
Adv Mater. 2023 May;35(19):e2212069. doi: 10.1002/adma.202212069. Epub 2023 Mar 26.
Although sonodynamic therapy (SDT) has shown promise for cancer treatment, the lack of efficient sonosensitizers (SSs) has limited the clinical application of SDT. Here, a new strategy is reported for designing efficient nano-sonosensitizers based on 2D nanoscale metal-organic layers (MOLs). Composed of Hf-oxo secondary building units (SBUs) and iridium-based linkers, the MOL is anchored with 5,10,15,20-tetra(p-benzoato)porphyrin (TBP) sensitizers on the SBUs to afford TBP@MOL. TBP@MOL shows 14.1- and 7.4-fold higher singlet oxygen ( O ) generation than free TBP ligands and Hf-TBP, a 3D nanoscale metal-organic framework, respectively. The O 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 iridium-based linkers and TBP SSs, which more efficiently harnesses broad-spectrum sonoluminescence. Anchoring TBP on the MOL surface also enhances the energy transfer between the excited sensitizer and ground-state triplet oxygen to increase O generation efficacy. In mouse models of colorectal and breast cancer, TBP@MOL demonstrates significantly higher SDT efficacy than Hf-TBP and TBP. This work uncovers a new strategy to design effective nano-sonosensitizers by facilitating energy transfer to efficiently capture broad-spectrum sonoluminescence and enhance O generation.
虽然声动力学疗法（SDT）在癌症治疗方面显示出了巨大的潜力，但缺乏高效的声敏剂（SSs）限制了 SDT 的临床应用。在此，报道了一种基于二维纳米尺度金属有机层（MOL）设计高效纳米声敏剂的新策略。该 MOL 由 Hf-氧代次级构筑单元（SBUs）和基于铱的连接体组成，SBUs 上锚定有 5,10,15,20-四（对苯甲酰基）卟啉（TBP）敏化剂，得到 TBP@MOL。TBP@MOL 的单线态氧（1 O ）生成效率分别比游离 TBP 配体和 3D 纳米尺度金属有机骨架 Hf-TBP 高 14.1 倍和 7.4 倍。TBP@MOL 通过将 TBP SSs 隔离在 MOL 的 SBUs 上，防止了敏化剂的聚集诱导猝灭，以及通过基于铱的激发态连接体和 TBP SSs 之间的三重态-三重态 Dexter 能量转移，更有效地利用了广谱声致发光，从而增强了 1 O 的生成。将 TBP 锚定在 MOL 表面还增强了激发敏化剂和基态三重态氧之间的能量转移，从而提高了 1 O 的生成效率。在结直肠癌和乳腺癌的小鼠模型中，TBP@MOL 显示出比 Hf-TBP 和 TBP 更高的 SDT 疗效。这项工作揭示了一种通过促进能量转移来设计有效纳米声敏剂的新策略，以有效地捕获广谱声致发光并增强 1 O 的生成。
