Work

Photothermally Tunable Nano‐Fusogen Enables Spatiotemporally Controlled Membrane Resealing after Traumatic Spinal Cord Injury

Year: 2026

Type: article

Abstract: Rapid restoration of membrane integrity represents a potential therapeutic approach to rescuing cells after traumatic spinal cord injury (TSCI). In contrast to endogenous repair mechanisms, which are often insufficient under severe injury conditions, synthetic membrane-resealing materials offer substantial potential but remain constrained by limited control over membrane interactions and functional activation. Here, we show that mild hyperthermia markedly enhances the membrane-resealing efficacy of polyethylene glycol (PEG), which may be associated with increased lipid bilayer fluidity and Annexin A1 expression. Based on these findings, we engineer a photothermal nano-fusogen by conjugating PEG and cholesterol-modified PEG onto gold nanorods, enabling targeted membrane insertion in vivo followed by near-infrared-triggered localized heating to achieve efficient membrane repair. In a rat TSCI model, a single intraspinal administration of the nano-fusogen combined with irradiation restores spinal cord compound action potentials, reduces lactate dehydrogenase release, suppresses cleaved caspase-3 expression, and was accompanied by higher expression of selected membrane-repair-associated genes. Longitudinal analyses further demonstrate improved hindlimb locomotor recovery and enhanced neuronal survival. This work establishes a photothermally tunable nano-fusogen platform for spatiotemporally controlled membrane repair and functional recovery after TSCI, with broader implications for acute injuries characterized by catastrophic membrane disruption.

Source: Small

DOI: 10.1002/smll.76667