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

Autor: Laomeephol C; 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., Tawinwung S; 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., Suppipat K; Cellular Immunotherapy Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; Department of Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand., Arunmanee W; Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand., Wang Q; Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208, USA., Amie Luckanagul J; 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.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jul 20; Vol. 660, pp. 124332. Date of Electronic Publication: 2024 Jun 10.
DOI: 10.1016/j.ijpharm.2024.124332
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jittima Amie Luckanagul is the co-founder and consultant of Nabsolute Co., Ltd., Bangkok, Thailand. The partial invention developed in this study has been filed for a Thai national patent under Chulalongkorn University and Nabsolute Co., Ltd. The other authors declare that they have no competing interests.].
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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