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Article

Gold Nanoparticles as a Platform for Delivery of Immunogenic Peptides to THP-1 Derived Macrophages: Insights into Nanotoxicity

by
Eduardo Zúñiga
1,
Braulio Contreras-Trigo
1,
Jorge Buchert
2,
Fabián Sáez-Ahumada
2,
Leonardo Hernández
2,
Víctor Fica-León
1,
Estefania Nova-Lamperti
2,
Bostjan Kobe
3,
Fanny Guzmán
4,
Víctor Diaz-García
1,
Enrique Guzmán-Gutiérrez
2 and
Patricio Oyarzún
1,*
1
Facultad de Ingeniería, Arquitectura y Diseño, Universidad San Sebastián, Concepción 4081339, Chile
2
Departamento de Bioquímica Clínica e Inmunología, Facultad de Farmacia, Universidad de Concepción, Concepción 4070386, Chile
3
School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, and Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia
4
Núcleo Biotecnología Curauma, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile
*
Author to whom correspondence should be addressed.
Vaccines 2025, 13(2), 119; https://doi.org/10.3390/vaccines13020119
Submission received: 14 December 2024 / Revised: 6 January 2025 / Accepted: 15 January 2025 / Published: 24 January 2025
(This article belongs to the Special Issue Innovations in Vaccine Technology)

Abstract

Background: Peptide-based nanovaccines have emerged as a promising strategy for combating infectious diseases, as they overcome the low immunogenicity that is inherent to short epitope-containing synthetic peptides. Gold nanoparticles (AuNPs) present several advantages as peptide nanocarriers, but a deeper understanding of the design criteria is paramount to accelerate the development of peptide-AuNPs nanoconjugates (p-AuNPs). Methods: Herein, we synthesized and characterized p-AuNPs of 23 nm (p-Au23) and 68 nm (p-Au68) with varying levels of peptide surface coverage and different peptide designs, investigating their effect on the cell viability (cell death and mitochondrial activity), cellular uptake, and cathepsin B activity in THP-1 macrophages. Results: p-Au23 proved no negative effect in the cell viability and high levels of nanoconjugate uptake, but p-Au68 induced strong toxicity to the cell line. The peptide sequences were successfully designed with spacer regions and a cell-penetrating peptide (pTAT) that enhanced cellular uptake and cathepsin B activity for p-Au23, while pTAT induced severe effects in the THP-1 viability (~40–60% cell death). Conclusions: These findings provide valuable insight into the design criteria of AuNPs and immunogenic peptides, along with nanotoxicity effects associated with AuNP size and surface charge in human monocyte-derived macrophages.
Keywords: peptide-based nanovaccination; epitope-based vaccination; gold nanoparticle; T-cell epitope; nanotoxicity; cathepsin B activity peptide-based nanovaccination; epitope-based vaccination; gold nanoparticle; T-cell epitope; nanotoxicity; cathepsin B activity

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MDPI and ACS Style

Zúñiga, E.; Contreras-Trigo, B.; Buchert, J.; Sáez-Ahumada, F.; Hernández, L.; Fica-León, V.; Nova-Lamperti, E.; Kobe, B.; Guzmán, F.; Diaz-García, V.; et al. Gold Nanoparticles as a Platform for Delivery of Immunogenic Peptides to THP-1 Derived Macrophages: Insights into Nanotoxicity. Vaccines 2025, 13, 119. https://doi.org/10.3390/vaccines13020119

AMA Style

Zúñiga E, Contreras-Trigo B, Buchert J, Sáez-Ahumada F, Hernández L, Fica-León V, Nova-Lamperti E, Kobe B, Guzmán F, Diaz-García V, et al. Gold Nanoparticles as a Platform for Delivery of Immunogenic Peptides to THP-1 Derived Macrophages: Insights into Nanotoxicity. Vaccines. 2025; 13(2):119. https://doi.org/10.3390/vaccines13020119

Chicago/Turabian Style

Zúñiga, Eduardo, Braulio Contreras-Trigo, Jorge Buchert, Fabián Sáez-Ahumada, Leonardo Hernández, Víctor Fica-León, Estefania Nova-Lamperti, Bostjan Kobe, Fanny Guzmán, Víctor Diaz-García, and et al. 2025. "Gold Nanoparticles as a Platform for Delivery of Immunogenic Peptides to THP-1 Derived Macrophages: Insights into Nanotoxicity" Vaccines 13, no. 2: 119. https://doi.org/10.3390/vaccines13020119

APA Style

Zúñiga, E., Contreras-Trigo, B., Buchert, J., Sáez-Ahumada, F., Hernández, L., Fica-León, V., Nova-Lamperti, E., Kobe, B., Guzmán, F., Diaz-García, V., Guzmán-Gutiérrez, E., & Oyarzún, P. (2025). Gold Nanoparticles as a Platform for Delivery of Immunogenic Peptides to THP-1 Derived Macrophages: Insights into Nanotoxicity. Vaccines, 13(2), 119. https://doi.org/10.3390/vaccines13020119

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