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Amino Compound-Synthesized Gold Nanoparticles for SARS-CoV-2 Antigen Delivery

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Author(s):
Rego, Layane Souza ; Favaro, Marianna Teixeira Pinho ; Rodrigues-Jesus, Monica Josiane ; Andreata-Santos, Robert ; Janini, Luiz Mario Ramos ; Seckler, Marcelo Martins ; Ferreira, Luis Carlos de Souza ; Azzoni, Adriano Rodrigues
Total Authors: 8
Document type: Journal article
Source: PHARMACEUTICS; v. 17, n. 9, p. 15-pg., 2025-09-17.
Abstract

Background: Gold nanoparticles (AuNPs) are a promising platform for vaccine antigen delivery due to their ability to stimulate both innate and adaptive immune responses. These effects depend strongly on physicochemical properties such as size, polydispersity, morphology, and surface charge, which are in turn determined by the synthesis method. While amino acids are often used as capping agents for AuNPs, their direct use as both reducing and stabilizing agents has been rarely investigated. Objectives: This study aimed to establish an ultrasound-assisted method for synthesizing AuNPs using amino compounds as both reducing and stabilizing agents, and assess their physicochemical characteristics, antigen-binding capacity, and immunogenicity. Methods: AuNPs were synthesized using L-cysteine, L-arginine, and cysteamine as dual reducing/stabilizing agents under ultrasonic conditions. The nanoparticles were combined with a recombinant receptor-binding domain (RBD) of SARS-CoV-2 and evaluated in mice for their ability to induce antibody responses. Results: The synthesized AuNPs exhibited hydrodynamic diameters ranging from 6.3 to 12.4 nm and zeta potentials from -40.5 to +36.5 mV, depending on the amino compound used. All formulations elicited robust anti-RBD IgG responses, but virus neutralization activity varied significantly. Notably, AuNP-arginine induced the strongest neutralizing response despite lower adsorption capacity and stability, suggesting that epitope preservation and antigen presentation quality were more decisive than antigen density. Conclusions: These findings underscore the importance of nanoparticle design in optimizing antigen presentation and highlight the potential of amino compound-synthesized AuNPs as effective antigen delivery vehicles for future vaccine development. (AU)

FAPESP's process: 23/01153-7 - Advances in COVID-19 vaccinology: development of new vaccine antigens with potential to mitigate the immunological escape of SARS-CoV-2
Grantee:Luis Carlos de Souza Ferreira
Support Opportunities: Regular Research Grants
FAPESP's process: 20/05204-7 - Development of SARS-CoV-2 auto-assembly protein-based nanovaccines
Grantee:Luis Carlos de Souza Ferreira
Support Opportunities: Regular Research Grants
FAPESP's process: 21/05661-1 - Virological characterization of Brazilian SARS-CoV-2 isolates and their neutralization capabilities by serum from previously infected and/or vaccinated individuals
Grantee:Robert Andreata Santos
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 20/08943-5 - Investigation of the hosts' induced elements in response to the immunisation with ChAdOx1 nCOV-19 vaccine in a Phase III Clinical Trial
Grantee:Luiz Mário Ramos Janini
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 23/16234-2 - Gold Nanoparticles as mRNA Delivery Vehicles in the context of Vaccines and Advanced Therapies
Grantee:Adriano Rodrigues Azzoni
Support Opportunities: Regular Research Grants
FAPESP's process: 20/10700-3 - Development os SAPN nanovaccines against SARS-CoV-2 using S and N as antigens
Grantee:Marianna Teixeira de Pinho Favaro
Support Opportunities: Scholarships in Brazil - Post-Doctoral