title: Labeling mesenchymal cells with DMSA-coated gold and iron oxide nanoparticles: assessment of biocompatibility and potential applications.
abstract: BACKGROUND
  Nanoparticles' unique features have been highly explored in cellular therapies. However, nanoparticles can be cytotoxic. The cytotoxicity can be overcome by coating the nanoparticles with an appropriated surface modification. Nanoparticle coating influences biocompatibility between nanoparticles and cells and may affect some cell properties. Here, we evaluated the biocompatibility of gold and maghemite nanoparticles functionalized with 2,3-dimercaptosuccinic acid (DMSA), Au-DMSA and γ-Fe2O3-DMSA respectively, with human mesenchymal stem cells. Also, we tested these nanoparticles as tracers for mesenchymal stem cells in vivo tracking by computed tomography and as agents for mesenchymal stem cells magnetic targeting.
  
  
  RESULTS
  Significant cell death was not observed in MTT, Trypan Blue and light microscopy analyses. However, ultra-structural alterations as swollen and degenerated mitochondria, high amounts of myelin figures and structures similar to apoptotic bodies were detected in some mesenchymal stem cells. Au-DMSA and γ-Fe2O3-DMSA labeling did not affect mesenchymal stem cells adipogenesis and osteogenesis differentiation, proliferation rates or lymphocyte suppression capability. The uptake measurements indicated that both inorganic nanoparticles were well uptaken by mesenchymal stem cells. However, Au-DMSA could not be detected in microtomograph after being incorporated by mesenchymal stem cells. γ-Fe2O3-DMSA labeled cells were magnetically responsive in vitro and after infused in vivo in an experimental model of lung silicosis.
  
  
  CONCLUSIONS
  In terms of biocompatibility, the use of γ-Fe2O3-DMSA and Au-DMSA as tracers for mesenchymal stem cells was assured. However, Au-DMSA shown to be not suitable for visualization and tracking of these cells in vivo by standard computed microtomography. Otherwise, γ-Fe2O3-DMSA shows to be a promising agent for mesenchymal stem cells magnetic targeting.
authors.affiliation: IB-Departamento de Genética e Morfologia, Universidade de Brasília-UNB, Campus Universitário Darcy Ribeiro-Asa Norte, Brasília, DF, CEP 70910-970, Brazil.
authors.forename: Luisa H A
authors.initials: LH
authors.lastname: Silva
authors.affiliation: IB-Departamento de Genética e Morfologia, Universidade de Brasília-UNB, Campus Universitário Darcy Ribeiro-Asa Norte, Brasília, DF, CEP 70910-970, Brazil.
authors.forename: Jaqueline R
authors.initials: JR
authors.lastname: da Silva
authors.affiliation: Instituto de Química, Universidade Federal de Goias, Goiânia, GO, Brazil.
authors.forename: Guilherme A
authors.initials: GA
authors.lastname: Ferreira
authors.affiliation: Instituto Nacional de Metrologia, Rio de Janeiro, RJ, Brazil.
authors.forename: Renata C
authors.initials: RC
authors.lastname: Silva
authors.affiliation: Instituto de Química, Universidade Federal de Goias, Goiânia, GO, Brazil.
authors.forename: Emilia C D
authors.initials: EC
authors.lastname: Lima
authors.affiliation: IB-Departamento de Genética e Morfologia, Universidade de Brasília-UNB, Campus Universitário Darcy Ribeiro-Asa Norte, Brasília, DF, CEP 70910-970, Brazil.
authors.forename: Ricardo B
authors.initials: RB
authors.lastname: Azevedo
authors.affiliation: IB-Departamento de Genética e Morfologia, Universidade de Brasília-UNB, Campus Universitário Darcy Ribeiro-Asa Norte, Brasília, DF, CEP 70910-970, Brazil. dmoliveira@unb.br.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Oliveira
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects; D005290:Ferric Compounds / Q000737:chemistry / Q000494:pharmacology; D006046:Gold / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D010316:Particle Size; D061251:Primary Cell Culture; D012829:Silicosis / Q000000981:diagnostic imaging* / Q000473:pathology; D013194:Staining and Labeling / Q000379:methods*; D004113:Succimer / Q000737:chemistry / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D006046:Gold; D004113:Succimer
keywords: Biocompatibility; Computed microtomography; DMSA-nanoparticles; Gold nanoparticles; Iron oxide nanoparticle; Magnetic targeting; Mesenchymal stem cells