Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury

被引:67
作者
Papastefanaki, Florentia [1 ]
Jakovcevski, Igor [2 ,3 ]
Poulia, Nafsika [1 ]
Djogo, Nevena [2 ]
Schulz, Florian [4 ]
Martinovic, Tamara [5 ]
Ciric, Darko [5 ]
Loers, Gabrielle [2 ]
Vossmeyer, Tobias [4 ]
Weller, Horst [6 ]
Schachner, Melitta [7 ]
Matsas, Rebecca [1 ]
机构
[1] Hellenic Pasteur Inst, Lab Cellular & Mol Neurobiol, Athens 11521, Greece
[2] Univ Hamburg, Univ Klinikum Hamburg Eppendorf, Zentrum Mol Neurobiol, Hamburg, Germany
[3] Univ Hosp Cologne, Expt Neurophysiol, Cologne, Germany
[4] Univ Hamburg, Inst Phys Chem, Hamburg, Germany
[5] Univ Belgrade, Sch Med, Inst Histol & Embryol, Belgrade, Serbia
[6] King Abdulaziz Univ, Fac Sci, Dept Chem, Jeddah, Saudi Arabia
[7] Shantou Univ, Coll Med, Ctr Neurosci, Guangdong, Peoples R China
关键词
CENTRAL-NERVOUS-SYSTEM; OXIDATIVE STRESS; SCHWANN-CELLS; IN-VIVO; REPAIR; REGENERATION; CONDUCTION; INHIBITION; NEUROTOXICITY; REMYELINATION;
D O I
10.1038/mt.2015.50
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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.
引用
收藏
页码:993 / 1002
页数:10
相关论文
共 51 条
[41]   Experimental strategies to promote spinal cord regeneration - an integrative perspective [J].
Schwab, JM ;
Brechtel, K ;
Mueller, CA ;
Failli, V ;
Kaps, HP ;
Tuli, SK ;
Schluesener, HJ .
PROGRESS IN NEUROBIOLOGY, 2006, 78 (02) :91-116
[42]   The Role of Functionalized Magnetic Iron Oxide Nanoparticles in the Central Nervous System Injury and Repair: New Potentials for Neuroprotection with Cerebrolysin Therapy [J].
Sharma, Hari Shanker ;
Menon, Preeti K. ;
Lafuente, Jose Vicente ;
Aguilar, Zoraida P. ;
Wang, Y. Andrew ;
Muresanu, Dafin Fior ;
Moessler, Herbert ;
Patnaik, Ranjana ;
Sharma, Aruna .
JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY, 2014, 14 (01) :577-595
[43]  
Shi YZ, 2010, NAT NANOTECHNOL, V5, P80, DOI [10.1038/nnano.2009.303, 10.1038/NNANO.2009.303]
[44]   THE RESTORATION OF CONDUCTION BY CENTRAL REMYELINATION [J].
SMITH, KJ ;
BLAKEMORE, WF ;
MCDONALD, WI .
BRAIN, 1981, 104 (JUN) :383-404
[45]   Stimulation of microglial metabotropic glutamate receptor mGlu2 triggers tumor necrosis factor α-induced neurotoxicity in concert with microglial-derived fas ligand [J].
Taylor, DL ;
Jones, F ;
Kubota, ESFCS ;
Pocock, JM .
JOURNAL OF NEUROSCIENCE, 2005, 25 (11) :2952-2964
[46]   Fluorescence Properties of Hydrophilic Semiconductor Nanoparticles with Tridentate Polyethylene Oxide Ligands [J].
Thiry, Marc ;
Boldt, Klaus ;
Nikolic, Marija S. ;
Schulz, Florian ;
Ijeh, Michael ;
Panicker, Andjana ;
Vossmeyer, Tobias ;
Weller, Horst .
ACS NANO, 2011, 5 (06) :4965-4973
[47]   Therapeutic interventions after spinal cord injury [J].
Thuret, Sandrine ;
Moon, Lawrence D. F. ;
Gage, Fred H. .
NATURE REVIEWS NEUROSCIENCE, 2006, 7 (08) :628-643
[48]   Inflammation and spinal cord injury: Infiltrating leukocytes as determinants of injury and repair processes [J].
Trivedi, Alpa ;
Olivas, Andrea D. ;
Noble-Haeusslein, Linda J. .
CLINICAL NEUROSCIENCE RESEARCH, 2006, 6 (05) :283-292
[49]   Interaction of NG2+ Glial Progenitors and Microglia/Macrophages from the Injured Spinal Cord [J].
Wu, Junfang ;
Yoo, Soonmoon ;
Wilcock, Donna ;
Lytle, Judith M. ;
Leung, Philberta Y. ;
Colton, Carol A. ;
Wrathall, Jean R. .
GLIA, 2010, 58 (04) :410-422
[50]   Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat [J].
Yang, LQ ;
Jones, NR ;
Blumbergs, PC ;
Van Den Heuvel, C ;
Moore, EJ ;
Manavis, J ;
Sarvestani, GT ;
Ghabriel, MN .
JOURNAL OF CLINICAL NEUROSCIENCE, 2005, 12 (03) :276-284