Multifunctional nanoparticle platform for targeted delivery and vaccines

  • iScience. 2025 May 7;28(6):112599. doi: 10.1016/j.isci.2025.112599.
Anja S Redecker  1 ,  Medea Neek  1 ,  Philip E J Smith  1 ,  James R Swartz  1  2
Affiliations
  • 1. Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
  • 2. Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
PMID: 40496813 DOI: 10.1016/j.isci.2025.112599
Abstract

We describe a versatile, targeted delivery platform based on the Hepatitis B core protein virus-like particle (VLP). Multiple protein mutations were combined with cell-free protein synthesis and anaerobic processing to enable reliable production of nanoparticles (NPs) loaded with single or multiple cargoes (typically with concentration factors >10ˆ4) and functionalized with single or multiple surface adducts. Our design supports multiple functional requirements while also enabling flexible and reliable production. Process yields are about 6 x 1013 NPs per mL of cell-free reaction; approximately 100-fold higher than current adeno-associated virus (AAV) yields and 8 times previously reported HBc VLP yields. We demonstrate platform feasibility and versatility by the surface display of a challenging-to-fold dengue fever antigen and by pharmacokinetic studies using whole-body mouse imaging. The platform supports rapid, parallel production of multiple product candidates to increase success rates for targeted therapeutics, gene therapies, imaging agents, and vaccines.

Keywords
Biochemistry; Biomaterials; Drug delivery system; Nanoparticles; Therapeutics.
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