The In Vivo Biological Fate of Protein Corona: A Comparative PET Study of the Fate of Soft and Hard Protein Corona in...

Area of Science:

• Nanomedicine
• Biomaterials Science
• Radiochemistry

Background:

• Protein corona formation on nanoparticles influences their biological fate.
• Distinguishing between soft and hard protein coronas is crucial for understanding nanoparticle behavior.
• Poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) are widely used in drug delivery.

Purpose of the Study:

• To investigate the in vivo biodistribution of soft and hard protein coronas formed on PLGA NPs.
• To compare the exchangeability and fate of soft versus hard protein coronas.
• To assess the impact of protein corona composition on nanoparticle biodistribution.

Main Methods:

• Radiolabeling (¹³¹I, ¹⁸F) of proteins and nanoparticles for imaging.
• In vitro assessment of protein corona exchangeability using gamma counting.
• In vivo biodistribution studies using positron emission tomography (PET) in mice.

Main Results:

• Polyethylenimine (PEI) functionalized PLGA NPs formed larger, more stable coronas than bovine serum albumin (BSA) functionalized PLGA NPs.
• Soft coronas exhibited higher exchangeability in vitro compared to hard coronas.
• In vivo, the soft corona followed free protein biodistribution, while the hard corona mimicked nanoparticle biodistribution, accumulating in the liver, spleen, and lungs.

Conclusions:

• The soft and hard protein coronas have distinct in vivo fates.
• The soft corona is readily exchanged with circulating proteins, while the hard corona remains associated with the nanoparticle.
• Understanding corona dynamics is essential for predicting nanoparticle behavior and optimizing nanomedicine design.