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用于脊髓损伤修复的碱性成纤维细胞生长因子的屏障穿透脂质体靶向递送。

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

作者信息

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

机构信息

Department of Arthroplasty, The First People's Hospital of Wenling, Affiliated Wenling Hospital, Wenzhou Medical University, Zhejiang, 317500, China.

Translational Medicine Laboratory, Affiliated Cixi Hospital, Wenzhou Medical University, Zhejiang, 325300, China.

出版信息

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

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 RKC 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.

摘要

纳米颗粒技术提供了一种非侵入性手段来递送碱性成纤维细胞生长因子(bFGF)以治疗脊髓损伤(SCI)。然而,bFGF无法在损伤部位积聚以及穿过血脊髓屏障(BSCB)的效率低下仍然是挑战。本研究描述了一种具有损伤病灶靶向和BSCB穿透能力的双靶向脂质体(bFGF@Lip-Cp&Rp),用于递送bFGF治疗SCI。将具有损伤病灶靶向能力的CAQK肽(Cp)和具有BSCB穿透能力的RKC肽(Rp)接枝到脂质体上,以制备灵活且非侵入性的药物递送系统。结果表明,双靶向脂质体能够显著穿过BSCB并在损伤部位积聚。在SCI早期,bFGF@Lip-Cp&Rp促进BSCB的修复并促进巨噬细胞的M2极化。定期递送bFGF@Lip-Cp&Rp可增加人脐静脉内皮细胞(HUVECs)的管腔形成和血管生成,改善损伤部位的微环境,抑制SCI大鼠的神经元凋亡和轴突萎缩。重要的是,持续用bFGF@Lip-Cp&Rp治疗可支持SCI大鼠肢体运动功能的恢复。总之,本研究表明,靶向损伤部位和穿透BSCB的脂质体可能是一种有前途的SCI治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d2e/9860515/52e0b0c28790/ga1.jpg

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