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IgG and fibrinogen driven nanoparticle aggregation

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Abstract

A thorough understanding of how proteins induce nanoparticle (NP) aggregation is crucial when designing in vitro and in vivo assays and interpreting experimental results. This knowledge is also crucial when developing nano-applications and formulation for drug delivery systems. In this study, we found that extraction of immunoglobulin G (IgG) from cow serum results in lower polystyrene NPs aggregation. Moreover, addition of isolated IgG or fibrinogen to fetal cow serum enhanced this aggregation, thus demonstrating that these factors are major drivers of NP aggregation in serum. Counter-intuitively, NP aggregation was inversely dependent on protein concentration; i.e., low protein concentrations induced large aggregates, whereas high protein concentrations induced small aggregates. Protein-induced NP aggregation and aggregate size were monitored by absorbance at 400 nm and dynamic light scattering, respectively. Here, we propose a mechanism behind the protein concentration dependent aggregation; this mechanism involves the effects of multiple protein interactions on the NP surface, surface area limitations, aggregation kinetics, and the influence of other serum proteins.

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Authors and Affiliations

  1. Department of Biochemistry and Structural Biology, Centre for Molecular Protein Science, Chemical Centre, Lund University, PO Box 124, SE-22100, Lund, Sweden

    Risto Cukalevski, Christopher J. Dunning & Tommy Cedervall

  2. Centre for Biological Engineering, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal

    Silvia A. Ferreira

  3. Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, BMC B11, 22184, Lund, Sweden

    Christopher J. Dunning

  4. Alligator Bioscience AB, Lund, Sweden

    Tord Berggård

Authors
  1. Risto Cukalevski
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  2. Silvia A. Ferreira
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  3. Christopher J. Dunning
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  4. Tord Berggård
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  5. Tommy Cedervall
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Correspondence to Tommy Cedervall.

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Cukalevski, R., Ferreira, S.A., Dunning, C.J. et al. IgG and fibrinogen driven nanoparticle aggregation. Nano Res. 8, 2733–2743 (2015). https://doi.org/10.1007/s12274-015-0780-4

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  • DOI: https://doi.org/10.1007/s12274-015-0780-4

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