PDF(Pubmed)
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.
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不能在损伤部位积聚以及穿过血-脊髓屏障(BSCB)的渗透效率低下仍然是一个挑战.本研究描述了一种双靶向脂质体（bFGF@Lip-Cp＆Rp），具有损伤病变靶向性和BSCB穿透能力，可将bFGF用于SCI治疗。将具有损伤病灶靶向能力的CAQK肽（Cp）和具有BSCB穿透能力的R2KC肽（Rp）接枝到脂质体上，以制备柔性和非侵入性的药物递送系统。结果表明，双靶向脂质体可以明显穿过BSCB并在损伤部位积聚。在SCI的早期阶段，bFGF@Lip-Cp和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和Rp可增加HUVECs管形成和血管生成，改善病变部位的微环境，抑制SCI大鼠神经元凋亡和轴突萎缩。重要的是,bFGF@Lip-Cp和Rp的连续治疗支持SCI大鼠肢体运动功能的恢复。总之,本研究提示损伤部位靶向和BSCB穿透性脂质体可能是治疗SCI的一种有前景的治疗方法.
