Plasma protein adsorption on Fe3O4-PEG nanoparticles activates the complement system and induces an inflammatory response

Background: Understanding of iron oxide nanoparticles (IONP) interaction with the body milieu is crucial to guarantee their efficiency and biocompatibility in nanomedicine. Polymer coating to IONP, with polyethyleneglycol (PEG) and polyvinylpyrrolidone (PVP), is an accepted strategy to prevent toxic...

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Bibliographic Details
Published in:International journal of nanomedicine 2019-01, Vol.14, p.2055-2067
Main Authors: Escamilla-Rivera, V, Solorio-Rodríguez, A, Uribe-Ramírez, M, Lozano, O, Lucas, S, Chagolla-López, A, Winkler, R, A De Vizcaya-Ruiz
Format: Article
Language:English
Subjects:
Evolution
Immune system
Lectins
Mass spectrometry
Nanoparticles
Nanostructured materials
Original Research
Peptides
Proteins
Proteomics
Scientific imaging
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Summary:Background: Understanding of iron oxide nanoparticles (IONP) interaction with the body milieu is crucial to guarantee their efficiency and biocompatibility in nanomedicine. Polymer coating to IONP, with polyethyleneglycol (PEG) and polyvinylpyrrolidone (PVP), is an accepted strategy to prevent toxicity and excessive protein binding. Aim: The aim of this study was to investigate the feature of IONP adsorption of complement proteins, their activation and consequent inflammatory response as a strategy to further elucidate their biocompatibility. Methods: Three types of IONP with different surface characteristics were used: bare (IONP-bare), coated with PVP (IONP-PVP) and PEG-coated (IONP-PEG). IONPs were incubated with human plasma and adsorbed proteins were identified. BALB/c mice were intravenously exposed to IONP to evaluate complement activation and proinflammatory response. Results: Protein corona fingerprinting showed that PEG surface around IONP promoted a selective adsorption of complement recognition molecules which would be responsible for the complement system activation. Furthermore, IONP-PEG activated in vitro, the complement system and induced a substantial increment of C3a and C4a anaphylatoxins while IONP-bare and IONP-PVP did not. In vivo IONP-PEG induced an increment in complement activation markers (C5a and C5b-9), and proinflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusion: The engineering of nanoparticles must incorporate the association between complement proteins and nanomedicines, which will regulate the immunostimulatory effects through a selective adsorption of plasma proteins and will enable a safer application of IONP in human therapy.
ISSN:1176-9114
1178-2013
DOI:10.2147/IJN.S192214