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Complement activation and cell uptake responses toward polymer-functionalized protein nanocapsules.

Nicholas M Molino1, Kateryna Bilotkach, Deborah A Fraser

  • 1Department of Chemical Engineering and Materials Science, University of California, Irvine, California 92697-2575, United States.

Biomacromolecules
|March 16, 2012
PubMed
Summary

Engineered protein nanocapsules show promise for bionanotechnology. PEGylation modulates cellular uptake and complement activation, offering tunable properties for nanomedicine applications.

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Area of Science:

  • Bionanotechnology
  • Protein engineering
  • Materials science

Background:

  • Self-assembling protein nanocapsules offer versatile platforms for bionanotechnology.
  • Engineering these structures allows for tailored surface functionalization and property modulation.

Purpose of the Study:

  • To engineer protein nanocapsules for site-directed functionalization.
  • To evaluate the impact of poly(ethylene glycol) (PEG) conjugation on nanoparticle properties, cellular uptake, and complement activation.

Main Methods:

  • Utilized the dodecahedral scaffold of the E2 subunit from pyruvate dehydrogenase.
  • Introduced non-native surface cysteines for site-directed functionalization.
  • Conjugated poly(ethylene glycol) (PEG) to the modified nanoparticles and assessed structural integrity, thermostability, cellular uptake, and complement activation (C4 depletion, C5a production).

Main Results:

  • Modified nanoparticles exhibited structural, assembly, and thermostability comparable to wild-type E2.
  • PEGylated nanoparticles remained stable up to 79.7 ± 1.8 °C.
  • PEGylation reduced cellular uptake by macrophages and breast cancer cells in a chain-length-dependent manner.
  • Non-PEGylated nanoparticles showed weak complement activation, while PEGylation moderately increased it.

Conclusions:

  • Engineered E2 protein nanocapsules are stable and amenable to functionalization.
  • PEGylation effectively modulates cellular uptake and induces low-level complement activation.
  • These findings highlight the potential of PEGylated E2 nanocapsules for tunable bionanotechnology applications.