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Serum-derived protein coronas affect nanoparticle interactions with brain cells.

Nabila Morshed1, Claire Rennie1, Wei Deng2

  • 1School of Life Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia.

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The protein corona significantly impacts how nanoparticles interact with brain cells. Understanding these protein coatings is crucial for advancing neuronanomedicine and developing effective nanotherapeutics.

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Area of Science:

  • Neuronanomedicine
  • Nanoparticle-cell interactions
  • Biomaterials science

Background:

  • Neuronanomedicine combines neuroscience and nanotherapeutics for brain treatments.
  • Clinical translation of neuronanomedicine is hindered by limited understanding of protein corona effects.
  • The protein corona influences nanoparticle behavior and interactions within biological systems.

Purpose of the Study:

  • To investigate the impact of serum-derived protein coronas on the interaction of polymeric nanoparticles with brain-derived cells.
  • To characterize the protein corona composition on poly(lactic-co-glycolic acid) (PLGA) and PLGA-polyethylene glycol (PLGA-PEG) nanoparticles.
  • To assess the effects of corona-coated nanoparticles on microglia, neuronal cells, and astrocytes.

Main Methods:

  • Formation of serum-derived protein coronas on PLGA and PLGA-PEG nanoparticles.
  • Characterization of protein coronas using liquid chromatography-mass spectrometry.
  • Assessment of nanoparticle internalization and cellular responses (cytokine release, viability) in primary brain cell cultures.

Main Results:

  • Distinct protein corona compositions were identified for PLGA (high globins, apolipoproteins) and PLGA-PEG (high protease inhibitors) nanoparticles.
  • Corona-coated PLGA nanoparticles were internalized by microglia and neuronal cells, but not astrocytes.
  • Nanoparticle internalization induced pro-inflammatory cytokine release and reduced neuronal viability, which was surprisingly rescued by corona-coated nanoparticles.

Conclusions:

  • The protein corona plays a critical role in mediating nanoparticle interactions with specific brain cell types.
  • Understanding protein corona composition is essential for designing effective neuronanomedicines.
  • Further research into corona-mediated effects could guide the development of targeted nanotherapeutics for neurological conditions.