Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs

β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug–protein conjugates that both induce the reactions and are immunologically reco...

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Autores principales: Violeta Gil-Ocaña, Isabel M. Jimenez, Cristobalina Mayorga, Inmaculada Doña, Jose Antonio Céspedes, Maria I. Montañez, Yolanda Vida, Maria J. Torres, Ezequiel Perez-Inestrosa
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/817313aa60f94f45a24d2100eb30b59e
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spelling oai:doaj.org-article:817313aa60f94f45a24d2100eb30b59e2021-12-03T06:21:56ZMultiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs1664-322410.3389/fimmu.2021.750109https://doaj.org/article/817313aa60f94f45a24d2100eb30b59e2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.750109/fullhttps://doaj.org/toc/1664-3224β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug–protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO2), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the in vitro clinical diagnostic practice. In this nano-inspired system biology, the synthetic dendrimer plays the role of the natural carrier protein, emulating its haptenation by drugs and amplifying the multivalence. Herein, we present the design and synthesis of new multivalent mono- and bi-epitope DeAn@SiO2, using amoxicillin and/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for in vitro applications. The suitable functionalization of nanoparticles allows the anchoring of DeAn, minimizing the nonspecific interactions and facilitating the effective exposure to specific IgE; while the larger interaction area increments the likelihood of capturing specific IgE. This achievement is particularly important for improving sensitivity of current immunoassays since IgE levels in BL allergic patients are very low. Our data suggest that these new nano-based platforms provide a suitable tool for testing IgE recognition to more than one BL simultaneously. Immunochemical studies evidence that mono and bi-epitope DeAn@SiO2 composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic–inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.Violeta Gil-OcañaVioleta Gil-OcañaIsabel M. JimenezIsabel M. JimenezCristobalina MayorgaCristobalina MayorgaCristobalina MayorgaInmaculada DoñaInmaculada DoñaJose Antonio CéspedesMaria I. MontañezMaria I. MontañezYolanda VidaYolanda VidaMaria J. TorresMaria J. TorresMaria J. TorresMaria J. TorresEzequiel Perez-InestrosaEzequiel Perez-InestrosaFrontiers Media S.A.articledendrimeric antigensilica nanoparticlesbiepitope nanocompositesdiagnostic testdrug allergypenicillinsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic dendrimeric antigen
silica nanoparticles
biepitope nanocomposites
diagnostic test
drug allergy
penicillins
Immunologic diseases. Allergy
RC581-607
spellingShingle dendrimeric antigen
silica nanoparticles
biepitope nanocomposites
diagnostic test
drug allergy
penicillins
Immunologic diseases. Allergy
RC581-607
Violeta Gil-Ocaña
Violeta Gil-Ocaña
Isabel M. Jimenez
Isabel M. Jimenez
Cristobalina Mayorga
Cristobalina Mayorga
Cristobalina Mayorga
Inmaculada Doña
Inmaculada Doña
Jose Antonio Céspedes
Maria I. Montañez
Maria I. Montañez
Yolanda Vida
Yolanda Vida
Maria J. Torres
Maria J. Torres
Maria J. Torres
Maria J. Torres
Ezequiel Perez-Inestrosa
Ezequiel Perez-Inestrosa
Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
description β-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current in vitro diagnostic tests have limited sensitivity, partly due to a poor understanding of in vivo drug–protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO2), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the in vitro clinical diagnostic practice. In this nano-inspired system biology, the synthetic dendrimer plays the role of the natural carrier protein, emulating its haptenation by drugs and amplifying the multivalence. Herein, we present the design and synthesis of new multivalent mono- and bi-epitope DeAn@SiO2, using amoxicillin and/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for in vitro applications. The suitable functionalization of nanoparticles allows the anchoring of DeAn, minimizing the nonspecific interactions and facilitating the effective exposure to specific IgE; while the larger interaction area increments the likelihood of capturing specific IgE. This achievement is particularly important for improving sensitivity of current immunoassays since IgE levels in BL allergic patients are very low. Our data suggest that these new nano-based platforms provide a suitable tool for testing IgE recognition to more than one BL simultaneously. Immunochemical studies evidence that mono and bi-epitope DeAn@SiO2 composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic–inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.
format article
author Violeta Gil-Ocaña
Violeta Gil-Ocaña
Isabel M. Jimenez
Isabel M. Jimenez
Cristobalina Mayorga
Cristobalina Mayorga
Cristobalina Mayorga
Inmaculada Doña
Inmaculada Doña
Jose Antonio Céspedes
Maria I. Montañez
Maria I. Montañez
Yolanda Vida
Yolanda Vida
Maria J. Torres
Maria J. Torres
Maria J. Torres
Maria J. Torres
Ezequiel Perez-Inestrosa
Ezequiel Perez-Inestrosa
author_facet Violeta Gil-Ocaña
Violeta Gil-Ocaña
Isabel M. Jimenez
Isabel M. Jimenez
Cristobalina Mayorga
Cristobalina Mayorga
Cristobalina Mayorga
Inmaculada Doña
Inmaculada Doña
Jose Antonio Céspedes
Maria I. Montañez
Maria I. Montañez
Yolanda Vida
Yolanda Vida
Maria J. Torres
Maria J. Torres
Maria J. Torres
Maria J. Torres
Ezequiel Perez-Inestrosa
Ezequiel Perez-Inestrosa
author_sort Violeta Gil-Ocaña
title Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
title_short Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
title_full Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
title_fullStr Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
title_full_unstemmed Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs
title_sort multiepitope dendrimeric antigen-silica particle composites as nano-based platforms for specific recognition of iges
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/817313aa60f94f45a24d2100eb30b59e
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