{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:17:03Z","timestamp":1786357023613,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T00:00:00Z","timestamp":1585008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Mesoporous silica nanoparticles (MSNPs) have the potential to be used as antigen carriers due to their high surface areas and highly ordered pore network. We investigated the adsorption and desorption of diphtheria toxoid as a proof-of-concept. Two series of nanoparticles were prepared\u2014(i) small pores (SP) (&lt;10 nm) and (ii) large pores (LP) (&gt;10 nm). SBA-15 was included as a comparison since this is commercially available and has been used in a large number of studies. External diameters of the particles ranged from 138 to 1509 nm, surface area from 632 to 1110 m2\/g and pore size from 2.59 to 16.48 nm. Antigen loading was assessed at a number of different ratios of silica-to-antigen and at 4 \u00b0C, 20 \u00b0C and 37 \u00b0C. Our data showed that protein adsorption by the SP series was in general consistently lower than that shown by the large pore series. Unloading was then examined at 4 \u00b0C, 20 \u00b0C and 37 \u00b0C and a pH 1.2, 4.5, 6.8 and 7.4. There was a trend amongst the LP particles towards the smallest pores showing the lowest release of antigen. The stability of the MSNP: antigen complex was tested at two different storage temperatures, and storage in solution or after lyophilization. After 6 months there was negligible release from any of the particles under any of the storage conditions. The particles were also shown not to cause hemolysis.<\/jats:p>","DOI":"10.3390\/pharmaceutics12030294","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T13:04:04Z","timestamp":1585055044000},"page":"294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["An Assessment of Mesoporous Silica Nanoparticle Architectures as Antigen Carriers"],"prefix":"10.3390","volume":"12","author":[{"given":"Xinyue","family":"Huang","sequence":"first","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen E","family":"Townley","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, Oxford University, John Radcliffe Hospital, Oxford OX3 9DU, UK"},{"name":"Department of Engineering Science, Oxford University, Parks Road, Oxford OX1 3PJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.vaccine.2015.01.073","article-title":"Safety of vaccine adjuvants: Focus on immunity","volume":"33","author":"Gould","year":"2015","journal-title":"Vaccine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.phrs.2015.08.003","article-title":"V accines adjuvants and autoimmunity","volume":"100","author":"Baker","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"B44","DOI":"10.1016\/j.vaccine.2015.02.073","article-title":"Communicating the role and value of vaccine adjuvants","volume":"33","author":"Gellin","year":"2015","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.nano.2014.09.014","article-title":"Mesoporous silica nanoparticles in drug delivery and biomedical applications","volume":"11","author":"Wang","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5167","DOI":"10.1039\/c3nr00357d","article-title":"Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery","volume":"5","author":"Mody","year":"2013","journal-title":"Nanoscale"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/j.ijpharm.2012.06.028","article-title":"Enhanced mucosal and systemic immune responses obtained by porous silica nanoparticles used as an oral vaccine adjuvant: Effect of silica architecture on immunological properties","volume":"436","author":"Wang","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","article-title":"Vaccine adjuvants: Putting Innate Immunity to work","volume":"33","author":"Coffman","year":"2010","journal-title":"Immunity"},{"key":"ref_8","first-page":"779","article-title":"Novel adjuvants & delivery vehicles for vaccines development: A road ahead","volume":"138","author":"Mohan","year":"2013","journal-title":"Indian J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1517\/14712598.8.2.235","article-title":"Safety and immunogenicity of a new hepatitis B vaccine for the protection of patients with renal insufficiency including pre-haemodialysis and haemodialysis patients","volume":"8","author":"Beran","year":"2008","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/S0264-410X(00)00499-0","article-title":"The adjuvanted influenza vaccines with novel adjuvants: Experience with the MF-59 adjuvanted vaccine","volume":"19","author":"Podda","year":"2001","journal-title":"Vaccine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Banzhoff, A., Gasparini, R., Laghi-Pasini, F., Staniscia, T., Durando, P., Montomoli, E., Capecchi, P., Di Giovanni, P., Sticchi, L., and Gentile, C. (2009). MF59-Adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults. PLoS ONE, 4.","DOI":"10.1371\/annotation\/5f2ae0fb-53f1-48c2-aa19-9114765ba029"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.vaccine.2005.08.095","article-title":"Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults","volume":"24","author":"Halperin","year":"2006","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6284","DOI":"10.1016\/j.vaccine.2009.01.040","article-title":"Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults","volume":"27","author":"Schwarz","year":"2009","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijpharm.2014.04.003","article-title":"A novel oil-in-water emulsion as a potential adjuvant for influenza virus: Development, characterization, stability and in vivo evaluation","volume":"468","author":"Deng","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"B14","DOI":"10.1016\/j.vaccine.2015.01.088","article-title":"New generation adjuvants- from empiricism to rational design","volume":"33","author":"Fox","year":"2015","journal-title":"Vaccine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3765","DOI":"10.1016\/j.vaccine.2014.05.037","article-title":"Freeze-thaw stress of alhydrogel alone is sufficient to reduce the immunogenicity of a recombinant hepatitis B vaccine containing native antigen","volume":"32","author":"Clapp","year":"2014","journal-title":"Vaccine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.2174\/092986711795933740","article-title":"Aluminium vaccine adjuvants: Are they safe?","volume":"18","author":"Tomljenovic","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/smll.200500274","article-title":"Ordered Mesoporous Silica SBA-15: A New Effective Adjuvant to Induce Antibody Response","volume":"2","author":"Mercuri","year":"2006","journal-title":"Small"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5496","DOI":"10.1039\/C6TB01131D","article-title":"Nanomaterial-based vaccine adjuvants","volume":"4","author":"Sun","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.4161\/hv.29589","article-title":"Applications of nanomaterials as vaccine adjuvants","volume":"10","author":"Zhu","year":"2014","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.colsurfb.2009.05.031","article-title":"Effect of surface charge and agglomerate degree of magnetic iron oxide nanoparticles on KB cellular uptake in vitro","volume":"73","author":"Ge","year":"2009","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7606","DOI":"10.1016\/j.biomaterials.2010.06.051","article-title":"Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods","volume":"31","author":"Qiu","year":"2010","journal-title":"Biomaterials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11051-019-4720-1","article-title":"Macrophage-like THP-1 cells show effective uptake of silica nanoparticles carrying inactivated diphtheria toxoid for vaccination","volume":"22","author":"Huang","year":"2020","journal-title":"J. Nanopartic. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1021\/ja01269a023","article-title":"Adsorption of Gases in Multimolecular Layers","volume":"60","author":"Brunauer","year":"1938","journal-title":"J. Am. Chem. Soc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1021\/ja01145a126","article-title":"The Determination of Pore Volume and Area Distributions in Porous Substances. I. Computations from Nitrogen Isotherms","volume":"73","author":"Barrett","year":"1951","journal-title":"J. Am. Chem. Soc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1039\/b304391f","article-title":"Rapid and high-capacity immobilization of enzymes based on mesoporous silicas with controlled morphologies","volume":"17","author":"Fan","year":"2003","journal-title":"Chem. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S0021-9258(18)45117-4","article-title":"Diphtheria toxin. I. Isolation and characterization of a toxic protein from culture filtrates of C. diptheriae","volume":"120","author":"Pappenheimer","year":"1937","journal-title":"J. Biol. Chem."},{"key":"ref_28","unstructured":"Sigma-Aldrich (2019). Sigma-Aldrich Product Specification, Sigma-Aldrich."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S1387-1811(01)00259-1","article-title":"Separation of biological molecules using mesoporous molecular sieves","volume":"44","author":"Kisler","year":"2001","journal-title":"Microporous Mesoporous Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/1743-422X-9-108","article-title":"Immunization of mice by Hollow Mesoporous Silica Nanoparticles as carriers of Porcine Circovirus Type 2 ORF2 Protein","volume":"9","author":"Guo","year":"2012","journal-title":"Virol. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8353","DOI":"10.1021\/jp102368s","article-title":"Functionalized Mesoporous Silica with Very Large Pores for Cellulase Immobilization","volume":"114","author":"Hartono","year":"2010","journal-title":"J. Phys. Chem. C"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1021\/acs.jpclett.5b00933","article-title":"Electrostatic Interactions Influence Protein Adsorption (but Not Desorption) at the Silica\u2013Aqueous Interface","volume":"6","author":"McUmber","year":"2015","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1098\/rsif.2012.0148","article-title":"Interfacial recognition of human prostate-specific antigen by immobilized monoclonal antibody: Effects of solution conditions and surface chemistry","volume":"9","author":"Zhao","year":"2012","journal-title":"J. R. Soc. Interface"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1006\/jcis.1996.0156","article-title":"Adsorption dynamics of IgG and Its F(ab\u2019)2 and Fc fragments studied by reflectometry","volume":"178","author":"Buijs","year":"1996","journal-title":"J. Colloid Interface Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1021\/la9601061","article-title":"Adsorption of \u00df-lactoglobulin A and B in relation to self-association: Effect of concentration and pH","volume":"13","author":"Elofsson","year":"1997","journal-title":"Langmuir"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/357216a0","article-title":"The crystal structure of diphtheria toxin","volume":"357","author":"Choe","year":"1992","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1002\/smll.200700005","article-title":"Tamanoi, Mesoporous silica nanoparticles as a delivery system for hydrophobic anticancer drugs","volume":"3","author":"Lu","year":"2007","journal-title":"Small"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14792","DOI":"10.1021\/ja0645943","article-title":"Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells","volume":"128","author":"Slowing","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1794","DOI":"10.1002\/smll.201000538","article-title":"Biocompatibility, biodistribution and drug-delivery efficiency of mesoporous silica nanoparticles for cancer therapy in animals","volume":"6","author":"Lu","year":"2010","journal-title":"Small"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1126\/science.1114397","article-title":"Toxic potential of materials at the nanolevel","volume":"311","author":"Nel","year":"2006","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.lwt.2013.12.037","article-title":"Characterization and in vitro bioavailability of \u03b2-carotene: Effects of microencapsulation method and food matrix","volume":"57","author":"Donhowe","year":"2014","journal-title":"LWT Food Sci. Technol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2","DOI":"10.5772\/58290","article-title":"Characterization and Comparison of Mesoporous Silica Particles for Optimized Drug Delivery","volume":"4","author":"Huang","year":"2014","journal-title":"Nanomater. Nanotechnol."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/3\/294\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:11:10Z","timestamp":1760173870000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/3\/294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":42,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["pharmaceutics12030294"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12030294","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]}}}