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Article

Covalent Functionalization of Layered Double Hydroxides to Generate Peptide-Based SARS-CoV-2 Nanovaccine

by
Alejandra E. Liñán-González
1,
Sayma A. Rodríguez-Montelongo
1,
Mariano J. García-Soto
1,
Daniela Gómez-Zarandona
1,
Susan Farfán-Castro
2,
Gabriela Palestino
1,
Raúl Ocampo-Pérez
1,
Erika Padilla-Ortega
1,*,
Omar González-Ortega
1,2,* and
Sergio Rosales-Mendoza
1,2,*
1
Centro de Investigación y Estudios de Posgrado, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Manuel Nava 6, Zona Universitaria, San Luis Potosí 78210, Mexico
2
Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud Biomedicina, Universidad Autónoma de San Luis Potosí, Av. Sierra Leona 550, Lomas 2a Sección, San Luis Potosí 78210, Mexico
*
Authors to whom correspondence should be addressed.
Materials 2025, 18(11), 2449; https://doi.org/10.3390/ma18112449
Submission received: 12 March 2025 / Revised: 11 May 2025 / Accepted: 19 May 2025 / Published: 23 May 2025

Abstract

Nanoclays have gained attention in biological applications due to their biocompatibility, low toxicity, and cost-effectiveness. Layered double hydroxides (LDHs) are synthetic nanoclays that have been used as adjuvants and antigen carriers in nanovaccines developed through passive bioconjugation. However, performing active bioconjugation to bind antigens covalently and generate subunit nanovaccines remains unexplored. In this study, we investigated the synthesis, functionalization, and active conjugation of LDH nanoparticles to produce subunit nanovaccines with peptides from SARS-CoV-2. The synthesis of Mg-Al LDHs via a coprecipitation and hydrothermal treatment rendered monodisperse particles averaging 100 nm. Their functionalization with (3-aminopropyl)triethoxysilane was better than it was with other organosilanes. Glutaraldehyde was used as a linker to bind lysine as a model biomolecule to establish the best conditions for reductive amination. Finally, two peptides, P2 and P5 (epitopes of the SARS-CoV-2 spike protein), were bound on the surface of the LDH to produce two subunit vaccine candidates, reaching peptide concentrations of 125 and 270 µg/mL, respectively. The particles were characterized using DLS, TEM, XRD, TGA, DSC, and FTIR. The cytotoxicity studies revealed that the conjugate with P2 was non-toxic up to 250 µg/mL, while the immunogenicity studies showed that this conjugate induced similar IgG titers to those reached when aluminum hydroxide was used as an adjuvant.
Keywords: layered double hydroxides; nanoclay; subunit nanovaccine; adjuvant; active conjugation layered double hydroxides; nanoclay; subunit nanovaccine; adjuvant; active conjugation

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MDPI and ACS Style

Liñán-González, A.E.; Rodríguez-Montelongo, S.A.; García-Soto, M.J.; Gómez-Zarandona, D.; Farfán-Castro, S.; Palestino, G.; Ocampo-Pérez, R.; Padilla-Ortega, E.; González-Ortega, O.; Rosales-Mendoza, S. Covalent Functionalization of Layered Double Hydroxides to Generate Peptide-Based SARS-CoV-2 Nanovaccine. Materials 2025, 18, 2449. https://doi.org/10.3390/ma18112449

AMA Style

Liñán-González AE, Rodríguez-Montelongo SA, García-Soto MJ, Gómez-Zarandona D, Farfán-Castro S, Palestino G, Ocampo-Pérez R, Padilla-Ortega E, González-Ortega O, Rosales-Mendoza S. Covalent Functionalization of Layered Double Hydroxides to Generate Peptide-Based SARS-CoV-2 Nanovaccine. Materials. 2025; 18(11):2449. https://doi.org/10.3390/ma18112449

Chicago/Turabian Style

Liñán-González, Alejandra E., Sayma A. Rodríguez-Montelongo, Mariano J. García-Soto, Daniela Gómez-Zarandona, Susan Farfán-Castro, Gabriela Palestino, Raúl Ocampo-Pérez, Erika Padilla-Ortega, Omar González-Ortega, and Sergio Rosales-Mendoza. 2025. "Covalent Functionalization of Layered Double Hydroxides to Generate Peptide-Based SARS-CoV-2 Nanovaccine" Materials 18, no. 11: 2449. https://doi.org/10.3390/ma18112449

APA Style

Liñán-González, A. E., Rodríguez-Montelongo, S. A., García-Soto, M. J., Gómez-Zarandona, D., Farfán-Castro, S., Palestino, G., Ocampo-Pérez, R., Padilla-Ortega, E., González-Ortega, O., & Rosales-Mendoza, S. (2025). Covalent Functionalization of Layered Double Hydroxides to Generate Peptide-Based SARS-CoV-2 Nanovaccine. Materials, 18(11), 2449. https://doi.org/10.3390/ma18112449

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