2. Academic Validation
  3. Precisely targeting of engineered nanovesicles to implanted scaffolds via click chemistry for microenvironment regulation in acute spinal cord injury

Precisely targeting of engineered nanovesicles to implanted scaffolds via click chemistry for microenvironment regulation in acute spinal cord injury

  • J Control Release. 2025 Oct 14;388(Pt 1):114321. doi: 10.1016/j.jconrel.2025.114321.
Xunqi Zhang 1,  Manning Zhu 1,  Jing Guo 1,  Jian Cao 1,  Juanjuan Zheng 1,  Jiahe Wu 2,  Weihang Zhou 1,  Xinchi Jiang 1,  Nan Wang 3,  Jiafu Mu 1,  Tianchen Huang 1,  Jian-Qing Gao 4
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
  • 2 Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, China.
  • 3 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou 310006, China.
  • 4 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China; Jinhua Institute of Zhejiang University, Jinhua 321002, China; State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China; Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. Electronic address: gaojianqing@zju.edu.cn.
PMID: 41101695 DOI: 10.1016/j.jconrel.2025.114321
Abstract

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.

Keywords

Click chemistry; Composite drug delivery system; Intranasal administration; Local implantation system; MSCs-extruded nanovesicles; Spinal cord injury.

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