2. Academic Validation
  3. Dual-engineered Treg-Exosome-IKVAV nanovesicles spatiotemporally sequentially regulate neuro-immune microenvironment to promote spinal cord injury repair

Dual-engineered Treg-Exosome-IKVAV nanovesicles spatiotemporally sequentially regulate neuro-immune microenvironment to promote spinal cord injury repair

  • J Nanobiotechnology. 2026 Jan 13;24(1):143. doi: 10.1186/s12951-025-03999-3.
Su Xinjin # 1,  Gu Changjiang # 1,  Zeng Feihui # 2,  Wei Ziheng 1,  Kong Qingjie 1,  Sun Weijin 3,  Zhu Chao 4,  Chen Xiongsheng 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
  • 2 Department of Endocrinology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
  • 3 Department of Nursing, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China. [email protected].
  • 4 Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. [email protected].
  • 5 Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 41530757 DOI: 10.1186/s12951-025-03999-3
Abstract

Spinal cord injury (SCI) repair remains a significant clinical challenge due to the imbalance of inflammatory microenvironment and insufficient neural regenerative ability. Current therapeutic approaches, such as pharmaceuticals, stem cell transplantation, and inorganic biomaterials, are limited by insufficient supply, poor bioactivity, and immunogenicity, severely limiting their clinical translation. To address these issues, we developed a biomimetic dual-engineered nanovesicles (Treg-Exo-IKVAV) by conjugating a neuroprotective IKVAV peptide motif with Treg-derived exosomes (Treg-Exo) using click chemistry. This system synergistically integrates the intrinsic immunomodulatory properties of Treg-Exo (early-stage anti-inflammation) with the neural regenerative capability of IKVAV, enabling spatiotemporally sequential regulation of neuro-regeneration. In vitro studies demonstrated that Treg-Exo-IKVAV suppressed macrophage-induced inflammatory responses by reprogramming macrophage polarization. Furthermore, Treg-Exo-IKVAV exerts dual direct and immunoregulatory effects on promoting neuronal differentiation of stem cells (NSCs). In vivo experiments revealed that Treg-Exo-IKVAV via tail vein injection precisely targeted and accumulated at the injured site. Subsequently, the functional assessments showed that Treg-Exo-IKVAV significantly enhanced motor functional recovery in SCI mice. Mechanistically, these nanovesicles reshaped the neuro-immune microenvironment through a two-phase mechanism: initial suppression of inflammation via Treg-derived anti-inflammatory signaling followed by activation of neuro-regenerative pathways mediated by IKVAV. This integrated "exosome-peptide" nanocomposite combining immunomodulation and neuronal regeneration provides a highly efficient and safe therapeutic solution for SCI.

Keywords

Exosome; IKVAV peptide; Neuro-immunoregulation; Spinal cord injury; Treg cell.

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