Mapping Nanoscale Protein-Corona Kinetics of DoE-Optimized Perfluorocarbon Encapsulated-PLGA Nanoparticles by In...

Area of Science:

• Nanotechnology
• Materials Science
• Biomedical Engineering

Background:

• Developing nanoparticle formulations requires understanding their behavior in biological environments.
• Characterizing the protein corona (PC) is crucial for predicting nanoparticle interactions.
• Integrated frameworks for nanoparticle formulation and PC analysis are limited.

Purpose of the Study:

• To develop and apply an integrated framework for formulating perfluoro-15-crown-5-ether-loaded poly(lactic-co-glycolic acid) nanoparticles (PFCE-PLGA NPs).
• To investigate the effects of formulation variables on nanoparticle characteristics and protein corona formation.
• To enable rational design of PFCE-PLGA NPs through nanoscale, time-resolved mapping.

Main Methods:

• Employed a two-phase workflow: single-factor screening and central composite design for formulation optimization.
• Utilized scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for morphology assessment.
• Applied synchrotron small-angle X-ray scattering (SAXS) for in situ, time-resolved protein corona analysis.

Main Results:

• Optimized formulation parameters (sonication, surfactant concentration, PFCE volume) influencing nanoparticle size, PDI, ζ-potential, and loading capacity.
• Resolved internal nanoparticle structure and quantified protein corona evolution under varying albumin concentrations using time-resolved SAXS.
• Demonstrated no significant cytotoxicity of PFCE-PLGA NPs in fibroblast assays.

Conclusions:

• The integrated framework successfully links processing variables to nanoscale structure and protein-mediated transformations.
• This approach provides a pathway for rational design of PFCE-PLGA nanoparticles.
• The study advances the understanding of nanoparticle-protein interactions for biomedical applications.