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Updated: Jun 26, 2026

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Surface-Capped Protein Nanoparticles for Nonviral Gene Delivery.

Fjorela Xhyliu1,2, Yao Yao1,3, Yeongun Ko1,2,4

  • 1Biointerfaces Institute, University of Michigan, Ann Arbor, Michigan, USA.

Advanced Materials (Deerfield Beach, Fla.)
|March 12, 2026
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Summary

We developed novel protein nanoparticles using electrohydrodynamic jetting for efficient gene delivery. These surface-capped protein nanoparticles (scPNPs) show high plasmid encapsulation and effective transfection in human T cells.

Keywords:
cell uptakeelectrohydrodynamic jetgene deliverynanoparticlespDNAtransfection

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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.