TY - JOUR
T1 - Plasma protein adsorption on Fe3O4-PEG nanoparticles activates the complement system and induces an inflammatory response
AU - Escamilla-Rivera, V.
AU - Solorio-Rodríguez, A.
AU - Uribe-Ramírez, M.
AU - Lozano, O.
AU - Lucas, S.
AU - Chagolla-López, A.
AU - Winkler, R.
AU - De Vizcaya-Ruiz, A.
N1 - Funding Information:
The authors would like to thank Dr Jaime Santoyo-Salazar and M.Sc. Roberto Mejía-Olvera, (Physics Department and Nanosciences and Nanotechnology Graduate program in Cinvestav-IPN), for the supply of the IONP-bare. RW was funded by the CONACyT Fronteras project 2015-2/814, the bilateral grant CONACyT-DFG 2016/277850 and PlanTECC.
Publisher Copyright:
© 2019 Escamilla-Rivera et al.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Complement
KW - Inflammatory response
KW - Iron oxide nanoparticles
KW - Protein corona
UR - http://www.scopus.com/inward/record.url?scp=85064947672&partnerID=8YFLogxK
U2 - 10.2147/IJN.S192214
DO - 10.2147/IJN.S192214
M3 - Article
C2 - 30988608
AN - SCOPUS:85064947672
SN - 1176-9114
VL - 14
SP - 2055
EP - 2067
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
ER -