Exosome-Loaded Pro-efferocytic Vascular Stent with Lp-PLA2‑Triggered Release for Preventing In-Stent Restenosis

• Published in: ACS nano Vol. 16; no. 9; pp. 14925 - 14941
• Main Authors: Zou, Dan, Yang, Ping, Liu, Jianan, Dai, Fanfan, Xiao, Yangyang, Zhao, Ansha, Huang, Nan
• Format: Journal Article
• Language: English
• Published: American Chemical Society 27.09.2022
• Subjects: atherosclerosis; stent; mesenchymal stem cell; exosome; Lp-PLA2; efferocytosis
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.2c05847

The efferocytosis defect is regarded as a pivotal event of atherosclerosis. The failure to clear apoptotic cells in atherosclerotic plaques under vascular stents causes a failure to resolve the inflammation underneath. However, efferocytosis repair is still confined to nonstenting therapeutics. Here, we identified a pro-efferocytotic agent and accordingly developed a bioresponsive pro-efferocytotic vascular stent aimed for poststenting healing. Exosomes derived from mesenchymal stem cells were found to be able to regulate efferocytosis via SLC2a1, STAT3/RAC1, and CD300a pathways and modulate foam cell formation processes through a CD36-mediated pathway. Pro-efferocytotic exosomes were encapsulated into liposome-based multivesicular chambers and grafted onto vascular stents. The multivesicular vesicles were able to release exosomes under the Lp-PLA2 environment. Compared to bare metal stents, exosome-stents in the presence of Lp-PLA2 enhanced the ratio of apoptotic cell clearance and reduced the neointimal thickness in the mal-efferocytotic rat model. Overall, we identified a pro-efferocytic agentexosomes that are able to regulate target cells via multiple signaling pathways and are good candidates to serve complex pathological environments, and this bioresponsive pro-efferocytotic vascular stent is an attractive approach for prevention of poststenting complications.