Dual-targeted microbubbles for atherosclerosis therapy: Inducing M1 macrophage apoptosis by inhibiting telomerase activity

作者：Wei Xue, Zhengan Huang, Yalan Huang, Kaifen Xiong, Yuanyuan Sheng, Xiaoxuan Lin, Xiaofang Zhong, Jiayu Ye, Yanbin Guo, Gulzira Arkin, Jinfeng Xu, Hongwen Fei, Yingying Liu · 发表于：Materials Today Bio · 年份：2025 · DOI：10.1016/j.mtbio.2025.101675 · 被引用次数：4 · 研究领域：Ultrasound and Hyperthermia Applications

The progression of atherosclerosis (AS) is closely associated with M1 macrophages. Although the activation of macrophage telomerase during plaque formation has been documented, targeted modulation strategies remain challenging. In this study, we developed a dual-target microbubble-delivery system (Ab-MMB 1532 ) encapsulating BIBR1532, a telomerase inhibitor, for the targeted therapy of AS. This system exhibited remarkable targeting capabilities towards M1 macrophages, with its targeting advantage notably accentuated under high shear forces. Mechanistically, Ab-MMB 1532 inhibited telomerase activity by downregulating telomerase reverse transcriptase (TERT) expression, subsequently inducing caspase-3-mediated apoptosis. Integrated multi-omics profiling revealed that the inhibition of the NF-κB pathway served as the central regulatory hub. In vivo studies further confirmed that Ab-MMB 1532 effectively targets and accumulates within AS lesions, promoting M1 macrophage apoptosis through the inhibition of the TERT/NF-κB signaling axis, and significantly reducing plaque burden (25.4 % reduction vs. controls, p < 0.001). In summary, our findings suggest a novel approach for telomerase-targeted therapy in AS. Schematic diagram displaying the Ab-MMB 1532 fabrication, targeting, and its anti-AS properties. • Dual-target microbubble drug-delivery system for AS is developed. • Targeting toward M1 macrophages is notably accentuated under high shear forces. • Ab-MMB 1532 downregulates telom...