UiO-66 MOFs-Based “Epi-Nano-Sonosensitizer” for Ultrasound-Driven Cascade Immunotherapy against B-Cell Lymphoma

作者：Zhihua Wang, Mingda Han, Yiqiao Wang, Ning Wang, Yilin Yang, Bingru Shao, Qiannan Miao, Zhan Shi, Fei Yan, Shouhua Feng · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c15761 · 被引用次数：39 · 研究领域：RNA modifications and cancer、Extracellular vesicles in disease、Ga2O3 and related materials

B-cell lymphoma (BCL) is a hematological malignancy with high heterogeneity and represents an aggressive proliferation of mature B-cells. Despite the initial success of traditional treatments for BCL in clinical trials, a majority of patients eventually develop resistance to therapy and have poor clinical outcomes. Epigenetic dysregulation is a major contributor to the pathogenesis of BCL, and therapies targeting epigenetic pathways is a promising alternative strategy for treating BCL. Herein, we developed a metal–organic framework (MOF)-based nano-sonosensitizer for ultrasound-driven cascade immunotherapy against BCL. The nano-sonosensitizer was synthesized by encapsulating copper complex of the m 6 A-mRNA demethylase inhibitor into UiO-66-NH 2, which possesses a Z-scheme heterostructure and allows efficient electron–hole pair separation for generating reactive oxygen species (ROS) under ultrasound activation. These CuR@UiO66 sonosensitizers were functionalized with mPEG-PO 3 and anti-CD19 antibody, and the resulting CRUPPA19 particles could specifically accumulate in the BCL tissue and also target lymphoma cells that infiltrated into the bone marrow. Once internalized, CRUPPA19 could induce intracellular ROS production and apoptosis under ultrasound irradiation. Subsequently, ultrasonic stimulation triggered autophagy-mediated release of Cu and Rhein from CRUPPA19, thereby increasing protein lipoylation and global mRNA methylation, which led to cuproptosis and the transcrip...