Surface-Capped Protein Nanoparticles for Nonviral Gene Delivery

Area of Science:

• Bioengineering
• Nanotechnology
• Gene Delivery

Background:

• Developing safe and efficient nonviral gene delivery systems is crucial in bioengineering.
• Existing nanoparticles face challenges in effective plasmid encapsulation and delivery.
• Protein-based nanoparticles offer a promising alternative with reduced toxicity.

Purpose of the Study:

• To report a novel protein-based nanoparticle platform for enhanced gene delivery.
• To demonstrate effective plasmid encapsulation and release using serum albumin nanoparticles.
• To optimize nanoparticle dosage for improved transfection efficiency.

Main Methods:

• Utilized electrohydrodynamic jetting to prepare protein-based nanoparticles from serum albumin.
• Employed interfacial complexation with a polycationic polymer for surface capping, avoiding chemical cross-linking.
• Investigated nanoparticle stability, payload capacity, cellular uptake pathways, and transfection efficiency in human T cells.

Main Results:

• Surface-capped protein nanoparticles (scPNPs) exhibited excellent stability at physiological pH for 12 days.
• Achieved high payload ratios (10-40% wt/wt) with 28-99 plasmids per scPNP.
• Demonstrated >95% cellular uptake via macropinocytosis and clathrin-mediated endocytosis, with increased dosage enhancing transfection rates.

Conclusions:

• scPNPs offer a stable, efficient, and safe nonviral gene delivery platform.
• The platform effectively encapsulates mRNA and facilitates transfection in primary human T cells, maintaining cell viability.
• This work advances nanoparticle design for gene therapy and highlights scPNPs' potential in cell therapies.