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
[1]   The Controlled Display of Biomolecules on Nanoparticles: A Challenge Suited to Bioorthogonal Chemistry [J].
Algar, W. Russ ;
Prasuhn, Duane E. ;
Stewart, Michael H. ;
Jennings, Travis L. ;
Blanco-Canosa, Juan B. ;
Dawson, Philip E. ;
Medintz, Igor L. .
BIOCONJUGATE CHEMISTRY, 2011, 22 (05) :825-858
[2]   Tenascin-R restricts posttraumatic remodeling of motoneuron innervation and functional recovery after spinal cord injury in adult mice [J].
Apostolova, Ivayla ;
Irintchev, Andrey ;
Schachner, Melitta .
JOURNAL OF NEUROSCIENCE, 2006, 26 (30) :7849-7859
[3]   Systemic Polyethylene Glycol Promotes Neurological Recovery and Tissue Sparing in Rats After Cervical Spinal Cord Injury [J].
Baptiste, Darryl C. ;
Austin, James W. ;
Zhao, William ;
Nahirny, Adrian ;
Sugita, Shuzo ;
Fehlings, Michael G. .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2009, 68 (06) :661-676
[4]   Kinetically Controlled Seeded Growth Synthesis of Citrate-Stabilized Gold Nanoparticles of up to 200 nm: Size Focusing versus Ostwald Ripening [J].
Bastus, Neus G. ;
Comenge, Joan ;
Puntes, Victor .
LANGMUIR, 2011, 27 (17) :11098-11105
[5]   Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment [J].
Beck, Kevin D. ;
Nguyen, Hal X. ;
Galvan, Manuel D. ;
Salazar, Desiree L. ;
Woodruff, Trent M. ;
Anderson, Aileen J. .
BRAIN, 2010, 133 :433-447
[6]   Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity [J].
Boisselier, Elodie ;
Astruc, Didier .
CHEMICAL SOCIETY REVIEWS, 2009, 38 (06) :1759-1782
[7]   TNFα mediates Schwann cell death by upregulating p75NTR expression without sustained activation of NFκB [J].
Boyle, K ;
Azari, MF ;
Cheema, SS ;
Petratos, S .
NEUROBIOLOGY OF DISEASE, 2005, 20 (02) :412-427
[8]   Chondroitinase ABC promotes functional recovery after spinal cord injury [J].
Bradbury, EJ ;
Moon, LDF ;
Popat, RJ ;
King, VR ;
Bennett, GS ;
Patel, PN ;
Fawcett, JW ;
McMahon, SB .
NATURE, 2002, 416 (6881) :636-640
[9]   Quantitative Evaluation of Cellular Uptake and Trafficking of Plain and Polyethylene Glycol-Coated Gold Nanoparticles [J].
Brandenberger, Christina ;
Muehlfeld, Christian ;
Ali, Zulqurnain ;
Lenz, Anke-Gabriele ;
Schmid, Otmar ;
Parak, Wolfgang J. ;
Gehr, Peter ;
Rothen-Rutishauser, Barbara .
SMALL, 2010, 6 (15) :1669-1678
[10]  
Brook GA, 1998, J NEUROSCI RES, V53, P51, DOI 10.1002/(SICI)1097-4547(19980701)53:1<51::AID-JNR6>3.0.CO