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A programmable platelet theranostic platform for adaptive multi-stage delivery and synergistic immunotherapy in atherosclerosis

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  • Yi Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Xueping Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ting Chen

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Jian Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

  • Ji Qi

    (Nankai University)

  • Wen Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College)

Abstract

Macrophages, along with the inflammatory and maladaptive immune responses they trigger, play crucial roles in the progression and rupture of atherosclerosis. We develop an adaptable platelet-protein platform tailored for the targeted delivery of both antioxidant nanocatalysts and TRAF6 inhibitor to advance synergistic therapy for atherosclerosis. The platform is constructed by assembling nanocatalyst- and TRAF6 inhibitor-loaded protein clusters with reactive oxygen species-cleavable linkers, then anchoring them onto the platelet surface for guided delivery to atherosclerotic plaques. Upon entering the reactive oxygen species-rich microenvironment, the platform disintegrates into ultra-small protein blocks, facilitating plaque penetration and selective macrophage internalization. The Mn-based nanocatalyst effectively scavenges various reactive oxygen species, while Mn ions concurrently enhance T1-weighted magnetic resonance imaging signals for diagnosis of atherosclerotic plaques. Meanwhile, the TRAF6 inhibitor blocks macrophage activation mediated by T lymphocytes. In a male mouse model of atherosclerosis, the versatile platform integrates cell-mediated natural targeting with adaptable size transformation for enhanced intraplaque penetration and unfavorable macrophage signaling reprogramming, offering opportunities for precise and multifaceted atherosclerosis therapy.

Suggested Citation

  • Yi Li & Xueping Li & Ting Chen & Jian Li & Ji Qi & Wen Li, 2025. "A programmable platelet theranostic platform for adaptive multi-stage delivery and synergistic immunotherapy in atherosclerosis," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61789-9
    DOI: 10.1038/s41467-025-61789-9
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    References listed on IDEAS

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