2. Academic Validation
  3. Surface functionalization of virus-like particles via bioorthogonal click reactions for enhanced cell-specific targeting

Surface functionalization of virus-like particles via bioorthogonal click reactions for enhanced cell-specific targeting

  • Int J Pharm. 2024 Jun 10:660:124332. doi: 10.1016/j.ijpharm.2024.124332.
Chavee Laomeephol 1,  Supannikar Tawinwung 2,  Koramit Suppipat 3,  Wanatchaporn Arunmanee 4,  Qian Wang 5,  Jittima Amie Luckanagul 6
Affiliations

Affiliations

  • 1 Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Center of Excellence in Biomaterial Engineering in Medical and Health, Chulalongkorn University, Bangkok 10330, Thailand.
  • 2 Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Cellular Immunotherapy Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
  • 3 Cellular Immunotherapy Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
  • 4 Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
  • 5 Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA.
  • 6 Center of Excellence in Biomaterial Engineering in Medical and Health, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand; Center of Excellence in Plant-produced Pharmaceuticals, Chulalongkorn University, Bangkok 10330, Thailand. Electronic address: Jittima.L@pharm.chula.ac.th.
PMID: 38866085 DOI: 10.1016/j.ijpharm.2024.124332
Abstract

Surface functionalization of nano drug carriers allows for precise delivery of therapeutic molecules to the target site. This technique involves attaching targeting molecules to the nanoparticle surface, facilitating selective interaction. In this study, we engineered virus-like particles (VLPs) to enhance their targeting capabilities. Azide groups incorporated on the lipid membranes of VLPs enabled bioorthogonal click reactions for conjugation with cycloalkyne-bearing molecules, providing efficient conjugation with high specificity. HIV-1 Gag VLPs were chosen due to their envelope, which allows host membrane component incorporation, and the Gag protein, which serves as a recognition motif for human T cells. This combination, along with antibody-mediated targeting, addresses the limitations of intracellular delivery to T cells, which typically exhibit low uptake of exogenous Materials. The selective uptake of Azide VLPs by CD3-positive T cells was evaluated in a co-culture system. Even without antibody conjugation, VLP uptake was enhanced in T cells, indicating their intrinsic targeting potential. Antibody conjugation further amplified this effect, demonstrating the synergistic benefits of the combined targeting approach. Our study shows that recombinant production of Azide functionalized VLPs results in engineered nanoparticles that can be easily modified using bioorthogonal click reactions, providing high specificity and versatility for conjugation with various molecules, making it applicable to a wide range of biological products.

Keywords

Antibody conjugation; Bioorthogonal click reactions; T cell delivery; Targeted drug delivery; Virus-like particles (VLPs).

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