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载姜黄素的聚膦腈纳米药物用于抗炎和神经再生,以改善脊髓损伤后的功能恢复。

Curcumin-Containing polyphosphazene nanodrug for Anti-Inflammation and nerve regeneration to improve functional recovery after spinal cord injury.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.

Department of Talent Highland, Center for Gut Microbiome Research, Med-X Institute, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China; School of Chemistry, Xi'an Key Laboratory of Sustainable Energy Material Chemistry, Xi'an Jiaotong University, Xi'an 710049, PR China.

出版信息

Int J Pharm. 2023 Jul 25;642:123197. doi: 10.1016/j.ijpharm.2023.123197. Epub 2023 Jul 4.

DOI:10.1016/j.ijpharm.2023.123197
PMID:37406950
Abstract

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1β, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/β-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

摘要

脊髓损伤 (SCI) 后,过度炎症的微环境和凋亡信号的激活是神经功能恢复的主要障碍。因此,长期抗炎已成为治疗 SCI 的有效策略。本研究通过将疏水性姜黄素 (CUR) 组装到交联聚磷腈 (PPZ) 中,并同时负载和配位多孔双金属聚合物,制备了一种载药效率高的含 CUR 的纳米系统 (FCTHPC),从而极大地提高了 CUR 的水溶性和生物相容性。当引导其生物活性时,纳米系统无细胞毒性。通过抑制促炎因子 (IL-1β、TNF-α 和 IL-6) 和凋亡蛋白 (C-caspase-3 和 Bax/Bcl-2) 的表达(可能通过激活 Wnt/β-catenin 通路实现),多功能 FCTHPC 可显著减轻 SCI 早期炎症和细胞凋亡对组织和细胞的损伤。此外,长期的体内研究表明,FCTHPC 可有效抑制神经胶质瘢痕的形成,同时促进神经再生和髓鞘形成,从而显著恢复脊髓功能。该研究强调了生物相容的基于 CUR 的纳米系统的前景,并为有效治疗 SCI 提供了一种新方法。

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