Department of Orthopedics, First Affiliated Hospital of Bengbu Medical College, 287 Changhuai Road, Bengbu, 233004, China.
Anhui Province Key Laboratory of Tissue Transplantation and School of Life Sciences, Bengbu Medical College, 2600 Donghai Road, Bengbu, 233030, China.
Tissue Eng Regen Med. 2023 Oct;20(6):879-892. doi: 10.1007/s13770-023-00567-4. Epub 2023 Aug 14.
The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration.
In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso-Beattie-Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining.
The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements.
Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.
脊髓损伤（SCI）后抑制性炎症微环境的形成仍然是神经再生的一大挑战。局部微环境恶化会加剧神经细胞死亡；因此，通过小分子药物重建有利的微环境是促进神经再生的一种有前途的策略。
本研究合成了负载姜黄素的胶束纳米粒（Cur-NPs）以提高姜黄素的生物利用度，并通过特征实验分析了 Cur-NPs 的物理化学性质。我们在大鼠体内建立了 SCI 模型，并通过 Basso-Beattie-Bresnahan 评分和后肢轨迹分析评估了后肢运动功能的恢复情况。我们还通过免疫荧光染色分析了 SCI 后的神经再生情况。
纳米粒实现了姜黄素的智能响应释放，同时提高了姜黄素的生物利用度。最重要的是，释放的姜黄素通过调节巨噬细胞从 M1 促炎表型向 M2 抗炎表型的极化，减轻了局部炎症。M2 型巨噬细胞通过分泌或表达促修复细胞因子来促进细胞分化、增殖、基质分泌和重排，从而减轻炎症反应。增强的炎症微环境支持神经元再生、神经髓鞘形成和减少疤痕形成。这些作用促进了大鼠的功能修复，主要表现为后肢运动的改善。
我们合成了 pH/温度双重敏感的 Cur-NPs。在提高药物生物利用度的同时，还能在 SCI 后形成的炎症微环境中实现智能响应释放。Cur-NPs 通过抗炎作用促进 SCI 后神经的再生和功能恢复，为 SCI 的修复提供了一种有前途的策略。
