Decoding Endothelial Glycocalyx-Nanoparticle Interactions via a Systematic Polymeric Nanoparticle Library and...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cell Biology

Background:

• Optimizing nanoparticle physicochemical properties is crucial for effective drug delivery.
• Understanding nanoparticle interactions with cells requires systematic investigation.

Purpose of the Study:

• To synthesize and characterize a library of polymeric nanoparticles varying in size and charge.
• To evaluate the impact of nanoparticle properties on cellular interactions, including cytotoxicity and uptake.
• To investigate the role of the cell glycocalyx in modulating these interactions.

Main Methods:

• High-throughput synthesis of 42 polymeric nanoparticles using RAFT polymerization and PISA.
• Characterization of nanoparticle cytotoxicity and uptake in endothelial cells with immature/mature glycocalyces.
• Semi-automated imaging and machine learning for single-cell nanoparticle uptake quantification.
• Assessment of protein corona formation and its effect on nanoparticle properties.

Main Results:

• Surface charge was a more dominant factor than hydrodynamic diameter in determining nanoparticle cytotoxicity and cellular uptake.
• Cationic nanoparticles showed higher toxicity and uptake, but cells with mature glycocalyces exhibited greater tolerance and uptake.
• The cell glycocalyx plays a protective and regulatory role in nanoparticle interactions.
• Protein corona formation altered nanoparticle surface charge and cellular interactions.

Conclusions:

• Nanoparticle surface charge is a critical design parameter for drug delivery.
• The cellular environment, particularly the glycocalyx, significantly influences nanoparticle behavior.
• Scalable analytical methods are essential for optimizing nanoparticle formulations for targeted delivery.