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Inside the Protein Corona: From Binding Parameters to Unstained Hard and Soft Coronas Visualization

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    Letter

    Inside the Protein Corona: From Binding Parameters to Unstained Hard and Soft Coronas Visualization
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    • Flávia E. Galdino
      Flávia E. Galdino
      Brazilian Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM) CP 6154, CEP 13083-970 Campinas, São Paulo, Brazil
      Institute of Chemistry, University of Campinas (UNICAMP), CP 6154, CEP 13083-970 Campinas, São Paulo,Brazil
      More by Flávia E. Galdino
    • Agustin S. Picco
      Agustin S. Picco
      Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Faultad de Ciencias Exactas, Universidad Nacional de La Plata—CONICET, 64 y Diag. 113, 1900 La Plata, Argentina
      More by Agustin S. Picco
    • Larissa B. Capeletti
      Larissa B. Capeletti
      Brazilian Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM) CP 6154, CEP 13083-970 Campinas, São Paulo, Brazil
      More by Larissa B. Capeletti
    • Jefferson Bettini
      Jefferson Bettini
      Brazilian Nanotechnology National Laboratory (LNNano), National Center for Research in Energy and Materials (CNPEM) CP 6154, CEP 13083-970 Campinas, São Paulo, Brazil
      More by Jefferson Bettini
    • Mateus B. Cardoso*
      Mateus B. Cardoso
      Brazilian Synchrotron Light Laboratory (LNLS), National Center for Research in Energy and Materials (CNPEM) CP 6154, CEP 13083-970 Campinas, São Paulo, Brazil
      Institute of Chemistry, University of Campinas (UNICAMP), CP 6154, CEP 13083-970 Campinas, São Paulo,Brazil
      *Email: [email protected]. Tel.: +55 19 3512 1045.
      More by Mateus B. Cardoso
      Orcidhttps://orcid.org/0000-0003-2102-1225
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    Nano Letters

    Cite this: Nano Lett. 2021, 21, 19, 8250–8257
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    https://doi.org/10.1021/acs.nanolett.1c02416
    Published September 23, 2021
    Copyright © 2021 American Chemical Society
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    Abstract

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    Proteins spontaneously adsorb on nanoparticle surfaces when injected into the bloodstream. It drastically modifies the nanoparticle’s fate and how they interact with organs and cells. Although this protein layer (protein corona) has been widely studied, the robustness of the most employed characterization methods and the visualization of its unstained fractions remain open questions. Here, synchrotron-based small-angle X-ray scattering was used to follow the corona formation and estimate binding parameters. At the same time, transmission electron microscopy under cryogenic conditions associated with cross-correlation image processing and energy-filtered transmission electron microscopy allowed to determine protein corona morphology and thickness together with the visualization of its unstained hard and soft fractions. The above-presented strategy shows tremendous potential for deciphering fundamental protein corona aspects and can contribute to rational medical nanoparticle engineering.

    Copyright © 2021 American Chemical Society

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.nanolett.1c02416.

    • Experimental methods; nanoparticles characterization; theories of protein–nanoparticle binding isotherms, DLS, and cumulants and NNLS analysis; equation for binding parameters by DLS and SAXS; protein corona DLS; influence of NNLS settings; DLS and SAXS analysis of corona free-nanoparticles; correlation curves (DLS) of aggregates; theory of Kratky and its correlation with fractional coverage; carbon intensity or intensity profile graphs; protein corona micrographs (PDF)

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    Nano Letters

    Cite this: Nano Lett. 2021, 21, 19, 8250–8257
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.nanolett.1c02416
    Published September 23, 2021
    Copyright © 2021 American Chemical Society
    Request reuse permissions

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