2. Academic Validation
  3. Transferrin-phosphatidylserine liposomes target TDP-43 and neuroinflammation in male mice with neuropathic pain

Transferrin-phosphatidylserine liposomes target TDP-43 and neuroinflammation in male mice with neuropathic pain

  • Nat Commun. 2025 Dec 12;16(1):11314. doi: 10.1038/s41467-025-66397-1.
Yingxin Liu 1,  Yue Wu 1,  Mali Zu 2 3,  Xingfan Li 2 3,  Jun Zhang 1,  Danning Wang 1,  Tianjiao Ji 4 5,  Jiamin Miao 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P. R. China.
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China.
  • 3 School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China.
  • 4 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center of Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, P. R. China. [email protected].
  • 5 School of Nanoscience and Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China. [email protected].
  • 6 Department of Anesthesiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, P. R. China. [email protected].
PMID: 41387431 DOI: 10.1038/s41467-025-66397-1
Abstract

Neuropathic pain (NP) is a debilitating condition driven by chronic neuroinflammation, where abnormal communication between microglia and astrocytes amplifies pain signaling. Current therapies offer limited benefit and primarily address symptoms rather than underlying mechanisms. Here, we show that transferrin- and phosphatidylserine-modified liposomes carrying a TDP-43 aggregation inhibitor (TF/PS/TDP-43-IN-1) effectively cross the blood-brain barrier, target glial cells, and modulate their activation states. In vitro, the formulation improved cell viability and promoted anti-inflammatory phenotypes. In vivo, studies conducted in male C57BL/6 J mice demonstrated significant alleviation of pain behaviors, reduced inflammatory cytokine expression, and suppression of the cGAS-STING pathway. These findings indicate that targeting TDP-43 aggregation with a nanocarrier system can reprogram glial interactions to relieve neuropathic pain. This strategy highlights a promising approach for developing targeted, disease-modifying therapies that act on key drivers of neuroinflammation.

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