Journal of controlled release : official journal of the Controlled Release SocietyOct 16, 2025

Precise delivery of engineered tiny particles to implanted supports for controlling the environment in acute spinal cord injury

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

The composite drug delivery system dGN&aNVs significantly enhanced local drug distribution and retention in spinal cord injury treatment.

Locally implanted scaffolds modified with dibenzocyclooctyne (DBCO) groups facilitate targeted drug delivery.
Intranasal administration of azide group-functionalized nanovesicles (aNVs) allows for continuous treatment.
The bio-orthogonal click chemistry reaction between aNVs and dGN improves drug localization at the injury site.
This system may promote recovery of hindlimb motor function and alleviate associated symptoms after spinal cord injury.
Tissue repair and regeneration are observed following treatment with the dGN&aNVs delivery system.

Simplified

Spinal cord injury (SCI) requires sufficient and sustained therapeutic intervention for microenvironment regulation in the acute phase. However, systemic drug administration is often ineffective due to non-specific distribution within the damaged spinal cord. While local implantation systems have gained attention for site-specific delivery, they are often constrained by spatial limitations and present challenges in designing sequential release profiles. Herein, we report the development of a composite drug delivery system integrating intranasal administration with local implantation. Specifically, the locally implanted scaffold was modified with dibenzocyclooctyne (DBCO) groups (dGN). Azide group-functionalized nanovesicles (aNVs), extruded from engineered mesenchymal stem cells, were continuously administered intranasally. aNVs accumulated within the lesion by undergoing a bio-orthogonal click chemistry reaction with dGN, which markedly enhanced their local distribution and retention. The composite drug delivery system, dGN&aNVs, effectively promoted acute microenvironmental regulation, hindlimb motor function recovery, associated symptoms alleviation, and tissue repair and regeneration following SCI in rats. This work presents a robust and minimally invasive platform for the precision-targeted therapy of SCI.

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Precise delivery of engineered tiny particles to implanted supports for controlling the environment in acute spinal cord injury

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