Charge-driven corona formation and nanoparticle cellular uptake: A microfluidic study on nanoparticle-protein...

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Protein corona formation on nanodrug carriers is a major obstacle to efficient drug delivery.
• The composition and structure of the protein corona are influenced by nanoparticle properties and environmental conditions.
• Understanding these influences is critical for optimizing nanocarrier design.

Purpose of the Study:

• To investigate the effect of nanoparticle surface charge on protein corona composition.
• To analyze how protein corona formation under dynamic (shear stress) versus static conditions affects cellular uptake.
• To provide insights for designing improved nanodrug delivery systems.

Main Methods:

• Utilized negatively charged DPE-PCL nanoparticles (DPNs) and positively charged DPE-PCL-Gly nanoparticles (DPGNs) as models.
• Simulated vascular shear conditions using microfluidic channels with serum.
• Employed SDS-PAGE and LC-MS/MS for detailed protein corona characterization.
• Conducted protein molecular docking simulations to analyze protein-protein interactions.

Main Results:

• Dynamic conditions amplified charge-dependent protein adsorption heterogeneity.
• Negatively charged DPNs exhibited broader protein adsorption under shear stress, while positively charged DPGNs showed reduced adsorption.
• Nanoparticle surface charge regulated inner-layer protein structure, influencing the overall protein corona via protein-protein interactions.
• Serum-derived protein corona hindered cellular uptake, but albumin pre-coating enhanced it.

Conclusions:

• Nanoparticle surface charge is a key determinant of protein corona composition and cellular interactions.
• Shear stress significantly alters protein adsorption behavior in a charge-dependent manner.
• Strategic surface modification and pre-coating can modulate protein corona formation and enhance nanocarrier efficacy for drug delivery.