Barrier-penetrating liposome targeted delivery of basic fibroblast growth factor for spinal cord injury repair

Fenzan Wu; Penghui Wang; Xiaojie Wei; Yanhong Yang; Abdullah Al Mamun; Xie Zhang; Yunsen Zhu; Tingting Mo; Hongyu Zhang; Chang Jiang; Jie Hu; Jian Xiao

doi:10.1016/j.mtbio.2023.100546

Barrier-penetrating liposome targeted delivery of basic fibroblast growth factor for spinal cord injury repair

Mater Today Bio. 2023 Jan 7:18:100546. doi: 10.1016/j.mtbio.2023.100546. eCollection 2023 Feb.

Authors

Fenzan Wu^{1

2

3}, Penghui Wang², Xiaojie Wei², Yanhong Yang³, Abdullah Al Mamun³, Xie Zhang⁴, Yunsen Zhu¹, Tingting Mo¹, Hongyu Zhang^{1

2

3}, Chang Jiang¹, Jie Hu⁵, Jian Xiao^{1

2

3}

Affiliations

¹ Department of Arthroplasty, The First People's Hospital of Wenling, Affiliated Wenling Hospital, Wenzhou Medical University, Zhejiang, 317500, China.
² Translational Medicine Laboratory, Affiliated Cixi Hospital, Wenzhou Medical University, Zhejiang, 325300, China.
³ School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang, 325035, China.
⁴ Department of Pharmacy, Ningbo Medical Treatment Center Li Huili Hospital, Zhejiang, 315040, China.
⁵ Stem Cell Translation Laboratory, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Shanxi, 030032, China.

Abstract

Nanoparticle technologies offer a non-invasive means to deliver basic fibroblast growth factor (bFGF) for the treatment of spinal cord injury (SCI). However, the inability of bFGF to accumulate at the injury site and inefficient penetration across the blood-spinal cord barrier (BSCB) remain challenges. The present study describes a dual-targeting liposome (bFGF@Lip-Cp&Rp) with injury lesion targeting and BSCB-penetrating capability to deliver bFGF for SCI treatment. The CAQK peptide (Cp) with injury lesion targeting ability and R₂KC peptide (Rp) with BSCB-penetrating capability were grafted onto the liposomes for a flexible and non-invasive drug delivery systems preparation. Results exhibit that the dual-targeted liposomes could significantly cross the BSCB and accumulate at the injury site. During the early stage of SCI, bFGF@Lip-Cp&Rp promotes repair of BSCB and facilitates M2-polarization of macrophages. Regular delivery of bFGF@Lip-Cp&Rp increase HUVECs tube formation and angiogenesis, ameliorate the microenvironment of lesion site, suppress the neuronal apoptosis and axonal atrophy in SCI rats. Importantly, continuous treatment of bFGF@Lip-Cp&Rp supports the restoration of limb motor function in SCI rats. In summary, this research implies that the injury site-targeting and BSCB-penetrating liposomes could be a promising therapeutic approach for the treatment of SCI.

Keywords: 1H NMR, 1H Nuclear magnetic resonance; Arg-1, Arginase 1; BBB, Basso-Beattie-Bresnahan; BSCB, Blood-spinal cord barrier; Basic fibroblast growth factor; CCK-8, Cell counting kit-8; CD31, Platelet endothelial cell adhesion molecule-1; CD86, Cluster of differentiation 86; CSPGs, Chondroitin sulfate proteoglycans; Cp, CAQK peptide; DSPE-PEG2000, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000]; DiI, 1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate; Drug delivery; FITC-BSA, Fluorescein isothiocyanate-labeled bovine serum albumin; GFAP, Glial fibrillary acidic protein; HUVECs, Human umbilical vein endothelial cells; IL-10, Interleukin 10; Liposome; Mal, Maleimide; NF-200, Neurofilament-200; NGF, Nerve growth factor; NT-3, Neurotrophin-3; Rp, R2KC peptide; SCI, Spinal cord injury; Spinal cord injury; TGF-β, Transforming growth factor-β; Target; VEGF-A, Vascular endothelial growth factor A; ZO-1, Zonulaoccludens 1; bFGF, Basic fibroblast growth factor.