Papastefanaki Florentia, Jakovcevski Igor, Poulia Nafsika, Djogo Nevena, Schulz Florian, Martinovic Tamara, Ciric Darko, Loers Gabrielle, Vossmeyer Tobias, Weller Horst, Schachner Melitta, Matsas Rebecca
Laboratory of Cellular and Molecular Neurobiology, Hellenic Pasteur Institute, Athens, Greece.
Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Universität Hamburg, Hamburg, Germany; Experimental Neurophysiology, University Hospital Cologne, Köln, Germany; Current address: German Center for Neurodegenerative Diseases, Bonn, Germany.
Mol Ther. 2015 Jun;23(6):993-1002. doi: 10.1038/mt.2015.50. Epub 2015 Mar 25.
Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.
哺乳动物中枢神经系统(CNS)在损伤后无法有效再生,这大多会导致不可逆的功能损害。金纳米颗粒(AuNPs)与组织相容性试剂(如聚乙二醇(PEG))结合用于药物递送很有前景。在中枢神经系统损伤模型中,给予PEG已引起人们对潜在治疗的兴趣,但毒性和低生物利用度阻碍了其临床应用。在此,我们表明在小鼠脊髓损伤后的早期阶段,经脊髓递送聚乙二醇功能化的40纳米金纳米颗粒有利于恢复。后肢运动功能的积极结果伴随着炎症反应减弱、运动神经元存活增加以及 spared或再生/发芽轴突的髓鞘形成增加。未观察到体重减轻、健康状况不佳或死亡率增加等不良反应。我们认为聚乙二醇-金纳米颗粒代表了一个具有治疗潜力的良好药物递送平台,如果将聚乙二醇-金纳米颗粒用作促进再生分子的载体,其治疗潜力可能会进一步增强。