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Immunol."],"abstract":"<jats:p>\u03b2-lactam antibiotics (BLs) are the drugs most frequently involved in drug hypersensitivity reactions. However, current <jats:italic>in vitro<\/jats:italic> diagnostic tests have limited sensitivity, partly due to a poor understanding of <jats:italic>in vivo<\/jats:italic> drug\u2013protein conjugates that both induce the reactions and are immunologically recognized. Dendrimeric Antigen-Silica particle composites (DeAn@SiO<jats:sub>2<\/jats:sub>), consisting on nanoparticles decorated with BL-DeAns are promising candidates for improving the <jats:italic>in vitro<\/jats:italic> 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@SiO<jats:sub>2<\/jats:sub>, using amoxicillin and\/or benzylpenicillin allergenic determinants as ligands. The homogeneous composition of nanoparticles provides high reproducibility and quality, which is critical for <jats:italic>in vitro<\/jats:italic> 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@SiO<jats:sub>2<\/jats:sub> composites could potentially allow the diagnosis of patients allergic to any of these drugs with a single test. These organic\u2013inorganic hybrid materials represent the basis for the development of a single screening for BL-allergies.<\/jats:p>","DOI":"10.3389\/fimmu.2021.750109","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T06:22:08Z","timestamp":1638512528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Multiepitope Dendrimeric Antigen-Silica Particle Composites as Nano-Based Platforms for Specific Recognition of IgEs"],"prefix":"10.3389","volume":"12","author":[{"given":"Violeta","family":"Gil-Oca\u00f1a","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel M.","family":"Jimenez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristobalina","family":"Mayorga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inmaculada","family":"Do\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Antonio","family":"C\u00e9spedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Monta\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Vida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezequiel","family":"Perez-Inestrosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,3]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1201\/9780429292750-3","article-title":"Nano-Biomedicine: A Next-Generation Tool for Effective and Safe Therapy","volume-title":"Nanobiotechnology","author":"Shrivastava","year":"2020"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2020.102316","article-title":"An Overview on Nanoparticles Used in Biomedicine and Their Cytotoxicity","volume":"61","author":"Nikzamir","year":"2021","journal-title":"J Drug Deliv Sci Technol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1039\/c2tb00301e","article-title":"Individual Inorganic Nanoparticles: Preparation, Functionalization and In Vitro Biomedical Diagnostic Applications","volume":"1","author":"Ladj","year":"2013","journal-title":"J Mater Chem B"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200703183","article-title":"Applications of Nanoparticles in Biology","volume":"20","author":"De","year":"2008","journal-title":"Adv Mater"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202001788","article-title":"Interactions Between Biomedical Micro-\/Nano-Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities","volume":"10","author":"Fu","year":"2021","journal-title":"Adv Healthc Mater"},{"key":"B6","article-title":"Drug Hypersensitivity Reactions: Response Patterns, Drug Involved, and Temporal Variations in a Large Series of Patients","volume":"22","author":"Do\u00f1a","year":"2012","journal-title":"J Investig Allergol Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1016\/j.jaip.2017.02.007","article-title":"Patients Taking Amoxicillin-Clavulanic can Become Simultaneously Sensitized to Both Drugs","volume":"5","author":"Salas","year":"2017","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/all.12886","article-title":"In Vitro Tests for Drug Hypersensitivity Reactions: An ENDA\/EAACI Drug Allergy Interest Group Position Paper","volume":"71","author":"Mayorga","year":"2016","journal-title":"Allergy Eur J Allergy Clin Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/all.13844","article-title":"Algorithm for Betalactam Allergy Diagnosis","volume":"74","author":"Do\u00f1a","year":"2019","journal-title":"Allergy"},{"key":"B10","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.jaci.2018.09.022","article-title":"Atanaskovic-Markovic, M.; Bonadonna, P.; Jares, E. 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