title: Biocompatibility of mannan nanogel--safe interaction with plasma proteins.
abstract: BACKGROUND
  Self-assembled mannan nanogels are designed to provide a therapeutic or vaccine delivery platform based on the bioactive properties of mannan to target mannose receptor expressed on the surface of antigen-presenting cells, combined with the performance of nanogels as carriers of biologically active agents.
  
  
  METHODS
  Proteins in the corona around mannan nanogel formed in human plasma were identified by mass spectrometry after size exclusion chromatography or centrifugation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Structural changes and time dependent binding of human apolipoprotein A-I (apoA-I) and human serum albumin (HSA) to mannan nanogel were studied using intrinsic tryptophan fluorescence and circular dichroism spectroscopy. The mannan nanogel effect on blood coagulation and fibrillation of Alzheimer's disease-associated amyloid β peptide and hemodialysis-associated amyloidosis β2 microglobulin was evaluated using thrombin generation assay or thioflavin T fluorescence assay, respectively.
  
  
  RESULTS
  The protein corona around mannan nanogel is formed through a slow process, is quite specific comprising apolipoproteins B-100, A-I and E and HSA, evolves over time, and the equilibrium is reached after hours to days. Structural changes and time dependent binding of apoA-I and HSA to mannan nanogel are minor. The mannan nanogel does not affect blood coagulation and retards the fibril formation.
  
  
  CONCLUSIONS
  Mannan nanogel has a high biosafety and biocompatibility, which is mandatory for nanomaterials to be used in biomedical applications.
  
  
  CONCLUSIONS
  Our research provides a molecular approach to evaluate the safety aspects of nanomaterials, which is of general concern in society and science.
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre for Biological Engineering, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal. silviarmferreira@gmail.com
authors.forename: Sílvia A
authors.initials: SA
authors.lastname: Ferreira
authors.forename: Cecilia
authors.initials: C
authors.lastname: Oslakovic
authors.forename: Risto
authors.initials: R
authors.lastname: Cukalevski
authors.forename: Birgitta
authors.initials: B
authors.lastname: Frohm
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlbäck
authors.forename: Sara
authors.initials: S
authors.lastname: Linse
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Gama
authors.forename: Tommy
authors.initials: T
authors.lastname: Cedervall
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D052160:Benzothiazoles; D001777:Blood Coagulation; D001798:Blood Proteins / Q000378:metabolism; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006801:Humans; D008351:Mannans / Q000378:metabolism*; D008422:Materials Testing; D000080385:Nanogels; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D012709:Serum Albumin / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013844:Thiazoles / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: C505693:APOA1 protein, human; D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; D052160:Benzothiazoles; D001798:Blood Proteins; D008351:Mannans; D000080385:Nanogels; D012709:Serum Albumin; D013844:Thiazoles; D001613:beta 2-Microglobulin; C413692:polyethylene glycol polyethyleneimine nanogel; C009462:thioflavin T; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D013917:Thrombin