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This work, reported by Xie Kun, Chen Liang, Zhu Xuesong, and Gu Yong from the Department of Orthopedics of the First Affiliated Hospital of Soochow University, focuses on the long-standing and unresolved core issue of uncontrolled immune microenvironment after spinal cord injury (SCI). The authors did not merely stop at the superficial classification of "pro-inflammatory / anti-inflammatory", but instead for the first time turned their attention to the "subcellular communication network" within macrophages, especially the pathological cross-talk between the endoplasmic reticulum (ER) and mitochondria (ER-mitochondria). The study found that in the context of strong oxidative stress after SCI, the abnormal calcium ion transport driven by Ero1α in the ER-mitochondria would "lock" the inflammatory phenotype of macrophages: ER stress enhancement → abnormal formation of MAMs → mitochondrial Ca²⁺ overload → mtDNA leakage → cGAS-STING-NFκB cascade activation → persistent inflammation and failure of neural regeneration.
Based on this mechanism, the authors constructed a "nanorobot" (BP@D/N) that masks the membrane of neutrophils, and precisely enriched it to the internal of macrophages in the injury area through systemic administration. Without causing secondary damage:
Reconstruct the ER-mitochondria communication mode; Block the Ero1α-Ca²⁺-mtDNA axis; Promote the transformation of macrophages from M1 to M2. Ultimately, it achieves the coordinated advancement of immune homeostasis restoration and neural regeneration. This work essentially proposes a new biological material treatment concept: no longer "sending signals", but "repairing the system"; not directly stimulating cells, but reconstructing their internal operating logic. It provides a system-level solution with solid mechanisms, convertible materials, and clear paths for irreversible SCI.
The relevant research was published in Nature Communications under the title "Camouflaged nanorobots target and regulate macrophage subcellular organelle crosstalk patterns to promote neural regeneration".
This chapter is not yet complete. Reprint: https://mp.weixin.qq.com/s/608ffDWOCLxmEj-v05T4ug
Original link: https://www.nature.com/articles/s41467-026-68636-5
