{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:02:31Z","timestamp":1790139751861,"version":"4.0.1"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Agency for Research and Development","award":["1221434"],"award-info":[{"award-number":["1221434"]}]},{"name":"National Agency for Research and Development","award":["250073"],"award-info":[{"award-number":["250073"]}]},{"award":["1221434"],"award-info":[{"award-number":["1221434"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"award":["250073"],"award-info":[{"award-number":["250073"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Australian Research Council Laureate","award":["FL180100109"],"award-info":[{"award-number":["FL180100109"]}],"id":[{"id":"https:\/\/ror.org\/05mmh0f86","id-type":"ROR","asserted-by":"crossref"}]},{"award":["FL180100109"],"award-info":[{"award-number":["FL180100109"]}],"id":[{"id":"https:\/\/ror.org\/05mmh0f86","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Health and Medical Research Council","award":["2025931"],"award-info":[{"award-number":["2025931"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2025931"],"award-info":[{"award-number":["2025931"]}],"id":[{"id":"https:\/\/ror.org\/011kf5r70","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Gold nanoparticles (AuNPs) are promising peptide carriers whose size and anisotropic morphology may influence their interactions with antigen-presenting cells. However, current knowledge of the morphology-dependent effects of AuNPs and the role of peptide design in human macrophage responses remains incomplete. Furthermore, most studies have been performed in THP-1-derived macrophages as the main in vitro macrophage-like model, despite human primary macrophages (HPMs) providing a more physiologically representative system. Anisotropic AuNPs with two morphologies, nanorods (AuNRs) and nanostars (AuNSs), each synthesized in two sizes, were characterized and conjugated to three influenza M2 T-cell-epitope constructs containing CD4+ (P1) and CD8+ T-cell epitopes (P2), individually, and both combined in a single multiepitope construct (P3), optimized for intracellular processing using a novel bioinformatics tool coupled to Predivac 3.0. THP-1-derived macrophages and HPMs were exposed to these nanoconjugates at a fixed particle number concentration of 10 pM for 24 h and assessed for mitochondrial activity, cell death, reactive oxygen species, endolysosomal acidification, proteasome activity, and cathepsin B activity. The identity of the nanoparticle carrier, defined by its geometry together with its specific surface chemistry, rather than the type of conjugated peptide, dominated the cellular response. AuNRs, particularly long rods, reduced mitochondrial activity, increased cell death, and enhanced bulk 20S proteasome activity in both models, even though at equal particle number they delivered 21- to 53-fold less gold mass and 6- to 12-fold less geometric surface area than AuNSs. The stimulatory effect induced by AuNRs-P1 and AuNRs-P2 on the proteasomal system may be associated with their specific peptide design features. By contrast, AuNSs preserved viability, maintained low oxidative stress, and produced strong acidification signals consistent with efficient trafficking to endolysosomal compartments; P2 and P3 conjugation further improved cytocompatibility and increased cathepsin B activity. HPMs were consistently more tolerant than THP-1 macrophages. The morphology-surface chemistry identity of the AuNP carrier is a key determinant of macrophage compatibility and of the relative engagement of the two degradative compartments assayed here. Functionalized AuNSs, especially P2- and P3-nanoconjugates, showed the best balance among biocompatibility, endolysosomal trafficking, and cathepsin B engagement. The proposed correspondence with MHC class I versus class II antigen-processing routes is a mechanistically informed hypothesis that remains to be further validated experimentally.<\/jats:p>","DOI":"10.3390\/ijms27188400","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:32:12Z","timestamp":1790083932000},"page":"8400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anisotropic Gold Nanoconjugates Bearing Immunoinformatically Designed T-Cell Epitope-Containing Peptides: Comparative Evaluation in THP-1 and Human Primary Macrophages"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2676-2866","authenticated-orcid":false,"given":"Braulio","family":"Contreras-Trigo","sequence":"first","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4081339, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Enrique","family":"Guzm\u00e1n-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda, Facultad de Farmacia, Universidad de Concepci\u00f3n, Concepci\u00f3n 4070386, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-6213","authenticated-orcid":false,"given":"Eduardo","family":"Z\u00fa\u00f1iga","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 380492, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4210-8311","authenticated-orcid":false,"given":"Fabi\u00e1n","family":"S\u00e1ez-Ahumada","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda, Facultad de Farmacia, Universidad de Concepci\u00f3n, Concepci\u00f3n 4070386, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0438-2987","authenticated-orcid":false,"given":"V\u00edctor","family":"Fica-Le\u00f3n","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4081339, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3003-0337","authenticated-orcid":false,"given":"Sim\u00f3n","family":"Guerrero","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santiago 380492, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2068-7669","authenticated-orcid":false,"given":"Dariela","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Ambiental, Facultad de Ciencias, Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"},{"name":"Centro de Investigaci\u00f3n en Biodiversidad y Ambientes Sustentables (CIBAS), Universidad Cat\u00f3lica de la Sant\u00edsima Concepci\u00f3n, Concepci\u00f3n 4030000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Andrea","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica Cl\u00ednica e Inmunolog\u00eda, Facultad de Farmacia, Universidad de Concepci\u00f3n, Concepci\u00f3n 4070386, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9828-6737","authenticated-orcid":false,"given":"Carmen","family":"Molina-Paris","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-9166","authenticated-orcid":false,"given":"Bostjan","family":"Kobe","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience, Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2343-4712","authenticated-orcid":false,"given":"V\u00edctor","family":"D\u00edaz-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4081339, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7305-1632","authenticated-orcid":false,"given":"Patricio","family":"Oyarz\u00fan","sequence":"additional","affiliation":[{"name":"Facultad de Ingenier\u00eda, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4081339, Chile"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41590-017-0007-9","article-title":"Emerging Viral Diseases from a Vaccinology Perspective: Preparing for the Next Pandemic","volume":"19","author":"Graham","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/S0140-6736(20)30553-5","article-title":"Health Security Capacities in the Context of COVID-19 Outbreak: An Analysis of International Health Regulations Annual Report Data from 182 Countries","volume":"395","author":"Kandel","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1007\/s11427-017-9241-3","article-title":"Human T-Cell Immunity against the Emerging and Re-Emerging Viruses","volume":"60","author":"Zhao","year":"2017","journal-title":"Sci. China Life Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/j.vaccine.2015.01.040","article-title":"A Bioinformatics Tool for Epitope-Based Vaccine Design That Accounts for Human Ethnic Diversity: Application to Emerging Infectious Diseases","volume":"33","author":"Oyarzun","year":"2015","journal-title":"Vaccine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1080\/21645515.2015.1094595","article-title":"Recombinant and Epitope-Based Vaccines on the Road to the Market and Implications for Vaccine Design and Production","volume":"12","author":"Kobe","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"D1053","DOI":"10.1093\/nar\/gkac1011","article-title":"The IPD-IMGT\/HLA Database","volume":"51","author":"Barker","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Song, X., Li, Y., Wu, H., Qiu, H., and Sun, Y. (2024). T-Cell Epitope-Based Vaccines: A Promising Strategy for Prevention of Infectious Diseases. Vaccines, 12.","DOI":"10.3390\/vaccines12101181"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Rosendahl Huber, S., van Beek, J., de Jonge, J., Luytjes, W., and van Baarle, D. (2014). T Cell Responses to Viral Infections\u2014Opportunities for Peptide Vaccination. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00171"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ribeiro, S.P., Rosa, D.S., Fonseca, S.G., Mairena, E.C., Post\u00f3l, E., Oliveira, S.C., Guilherme, L., Kalil, J., and Cunha-Neto, E. (2010). A Vaccine Encoding Conserved Promiscuous HIV CD4 Epitopes Induces Broad T Cell Responses in Mice Transgenic to Multiple Common HLA Class II Molecules. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011072"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1021\/acs.chemrev.9b00472","article-title":"Peptide-Based Vaccines: Current Progress and Future Challenges","volume":"120","author":"Malonis","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fujita, Y., and Taguchi, H. (2017). Nanoparticle-Based Peptide Vaccines. Micro and Nanotechnology in Vaccine Development, Elsevier.","DOI":"10.1016\/B978-0-323-39981-4.00008-7"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gregory, A.E., Titball, R., and Williamson, D. (2013). Vaccine Delivery Using Nanoparticles. Front. Cell. Infect. Microbiol., 3.","DOI":"10.3389\/fcimb.2013.00013"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.ddtec.2021.02.001","article-title":"Gold Nanoparticle-Based Platforms for Vaccine Development","volume":"38","author":"Lay","year":"2020","journal-title":"Drug Discov. Today Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41541-021-00330-7","article-title":"Protein-Based Antigen Presentation Platforms for Nanoparticle Vaccines","volume":"6","author":"Nguyen","year":"2021","journal-title":"npj Vaccines"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1021\/nl052396o","article-title":"Determining the Size and Shape Dependence of Gold Nanoparticle Uptake into Mammalian Cells","volume":"6","author":"Chithrani","year":"2006","journal-title":"Nano Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1186\/s11671-018-2728-6","article-title":"Insight into Cellular Uptake and Intracellular Trafficking of Nanoparticles","volume":"13","author":"Foroozandeh","year":"2018","journal-title":"Nanoscale Res. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1039\/C6CS00636A","article-title":"Cellular Uptake of Nanoparticles: Journey Inside the Cell","volume":"46","author":"Behzadi","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1039\/D0CS01127D","article-title":"Understanding Nanoparticle Endocytosis to Improve Targeting Strategies in Nanomedicine","volume":"50","author":"Susnik","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1021\/nn2000756","article-title":"Differential Uptake of Functionalized Polystyrene Nanoparticles by Human Macrophages and a Monocytic Cell Line","volume":"5","author":"Lunov","year":"2011","journal-title":"ACS Nano"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3073","DOI":"10.1021\/nn100262h","article-title":"Rapid Uptake of Gold Nanorods by Primary Human Blood Phagocytes and Immunomodulatory Effects of Surface Chemistry","volume":"4","author":"Bartneck","year":"2010","journal-title":"ACS Nano"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1021\/nl070363y","article-title":"Elucidating the Mechanism of Cellular Uptake and Removal of Protein-Coated Gold Nanoparticles of Different Sizes and Shapes","volume":"7","author":"Chithrani","year":"2007","journal-title":"Nano Lett."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Z\u00fa\u00f1iga, E., Contreras-Trigo, B., Buchert, J., S\u00e1ez-Ahumada, F., Hern\u00e1ndez, L., Fica-Le\u00f3n, V., Nova-Lamperti, E., Kobe, B., Guzm\u00e1n, F., and Diaz-Garc\u00eda, V. (2025). Gold Nanoparticles as a Platform for Delivery of Immunogenic Peptides to THP-1 Derived Macrophages: Insights into Nanotoxicity. Vaccines, 13.","DOI":"10.3390\/vaccines13020119"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jaut.2014.07.005","article-title":"Epitope-Based Approaches to a Universal Influenza Vaccine","volume":"54","author":"Gottlieb","year":"2014","journal-title":"J. Autoimmun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s00005-010-0067-0","article-title":"CD4+ T Cell Epitope Discovery and Rational Vaccine Design","volume":"58","author":"Rosa","year":"2010","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"102372","DOI":"10.1016\/j.nano.2021.102372","article-title":"Synthesis and Immunogenicity Assessment of a Gold Nanoparticle Conjugate for the Delivery of a Peptide from SARS-CoV-2","volume":"34","author":"Palestino","year":"2021","journal-title":"Nanomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jconrel.2017.04.024","article-title":"Effects of Gold Nanoparticle-Based Vaccine Size on Lymph Node Delivery and Cytotoxic T-Lymphocyte Responses","volume":"256","author":"Kang","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5874","DOI":"10.1021\/acsnano.0c01021","article-title":"One Peptide for Them All: Gold Nanoparticles of Different Sizes Are Stabilized by a Common Peptide Amphiphile","volume":"14","author":"Egorova","year":"2020","journal-title":"ACS Nano"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/rb\/rbv024","article-title":"Effects of the Physicochemical Properties of Gold Nanostructures on Cellular Internalization","volume":"2","author":"Gong","year":"2015","journal-title":"Regen. Biomater."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1039\/D2RA06888E","article-title":"Effects of Morphology and Size of Nanoscale Drug Carriers on Cellular Uptake and Internalization Process: A Review","volume":"13","author":"Zhang","year":"2023","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1002\/smll.200801546","article-title":"Cellular Uptake and Cytotoxicity of Gold Nanorods: Molecular Origin of Cytotoxicity and Surface Effects","volume":"5","author":"Alkilany","year":"2009","journal-title":"Small"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11398","DOI":"10.1038\/srep11398","article-title":"Surface Chemistry but Not Aspect Ratio Mediates the Biological Toxicity of Gold Nanorods In Vitro and In Vivo","volume":"5","author":"Wan","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1900799","DOI":"10.1002\/smtd.201900799","article-title":"Effects of Cetyltrimethylammonium Bromide on the Toxicity of Gold Nanorods Both In Vitro and In Vivo: Molecular Origin of Cytotoxicity and Inflammation","volume":"4","author":"Jia","year":"2020","journal-title":"Small Methods"},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"20220462","DOI":"10.1098\/rsif.2022.0462","article-title":"Role of Particle Local Curvature in Cellular Wrapping","volume":"19","author":"Khosravanizadeh","year":"2022","journal-title":"J. R. Soc. Interface"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Vandebriel, R.J., Remy, S., Vermeulen, J.P., Hurkmans, E.G.E., Kevenaar, K., Bast\u00fas, N.G., Pelaz, B., Soliman, M.G., Puntes, V.F., and Parak, W.J. (2022). Pathways Related to NLRP3 Inflammasome Activation Induced by Gold Nanorods. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105763"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5895","DOI":"10.2147\/IJN.S314643","article-title":"Gold Nanoparticles Dissolve Extracellularly in the Presence of Human Macrophages","volume":"16","author":"McCarrick","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3827","DOI":"10.1038\/s41598-017-04229-z","article-title":"The Effect of Shape on Cellular Uptake of Gold Nanoparticles in the Forms of Stars, Rods, and Triangles","volume":"7","author":"Xie","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Tedesco, S., De Majo, F., Kim, J., Trenti, A., Trevisi, L., Fadini, G.P., Bolego, C., Zandstra, P.W., Cignarella, A., and Vitiello, L. (2018). Convenience versus Biological Significance: Are PMA-Differentiated THP-1 Cells a Reliable Substitute for Blood-Derived Macrophages When Studying in Vitro Polarization?. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00071"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2428","DOI":"10.1021\/acsnano.6b06245","article-title":"Phenotype Determines Nanoparticle Uptake by Human Macrophages from Liver and Blood","volume":"11","author":"MacParland","year":"2017","journal-title":"ACS Nano"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4572","DOI":"10.1039\/D4NA00104D","article-title":"The Impact of Macrophage Phenotype and Heterogeneity on the Total Internalized Gold Nanoparticle Counts","volume":"6","author":"Lee","year":"2024","journal-title":"Nanoscale Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6031776","DOI":"10.1155\/2022\/6031776","article-title":"The In Vitro Immunomodulatory Effects of Gold Nanocomplex on THP-1-Derived Macrophages","volume":"2022","author":"Abuarqoub","year":"2022","journal-title":"J. Immunol. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1038\/srep01326","article-title":"Microscopic Analysis of the Interaction of Gold Nanoparticles with Cells of the Innate Immune System","volume":"3","author":"Sumbayev","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ong, K.J., MacCormack, T.J., Clark, R.J., Ede, J.D., Ortega, V.A., Felix, L.C., Dang, M.K.M., Ma, G., Fenniri, H., and Veinot, J.G.C. (2014). Widespread Nanoparticle-Assay Interference: Implications for Nanotoxicity Testing. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090650"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s00018-011-0657-y","article-title":"The Role of the Proteasome in the Generation of MHC Class I Ligands and Immune Responses","volume":"68","author":"Sijts","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/S1074-7613(00)80447-1","article-title":"Localization, Quantitation, and In Situ Detection of Specific Peptide\u2013MHC Class I Complexes Using a Monoclonal Antibody","volume":"6","author":"Porgador","year":"1997","journal-title":"Immunity"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4049\/jimmunol.0903399","article-title":"Proteases in MHC Class I Presentation and Cross-Presentation","volume":"184","author":"Rock","year":"2010","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1021\/acs.biochem.3c00139","article-title":"Distinct Cleavage Properties of Cathepsin B Compared to Cysteine Cathepsins Enable the Design and Validation of a Specific Substrate for Cathepsin B over a Broad pH Range","volume":"62","author":"Yoon","year":"2023","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12824","DOI":"10.1074\/jbc.M513331200","article-title":"Substrate Profiling of Cysteine Proteases Using a Combinatorial Peptide Library Identifies Functionally Unique Specificities","volume":"281","author":"Choe","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S1074-7613(00)80176-4","article-title":"Proteolysis in MHC Class II Antigen Presentation: Who\u2019s in Charge?","volume":"12","author":"Villadangos","year":"2000","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.1073\/pnas.95.8.4516","article-title":"Cathepsins B and D Are Dispensable for Major Histocompatibility Complex Class II-Mediated Antigen Presentation","volume":"95","author":"Deussing","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nri1149","article-title":"MHC-Guided Processing: Binding of Large Antigen Fragments","volume":"3","author":"Sercarz","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Oyarzun, P., Kashyap, M., Fica, V., Salas-Burgos, A., Gonzalez-Galarza, F.F., McCabe, A., Jones, A.R., Middleton, D., and Kobe, B. (2021). A Proteome-Wide Immunoinformatics Tool to Accelerate T-Cell Epitope Discovery and Vaccine Design in the Context of Emerging Infectious Diseases: An Ethnicity-Oriented Approach. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.598778"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/protein\/4.2.155","article-title":"Correlation between Stability of a Protein and Its Dipeptide Composition: A Novel Approach for Predicting in Vivo Stability of a Protein from Its Primary Sequence","volume":"4","author":"Guruprasad","year":"1990","journal-title":"Protein Eng."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0022-2836(82)90515-0","article-title":"A Simple Method for Displaying the Hydropathic Character of a Protein","volume":"157","author":"Kyte","year":"1982","journal-title":"J. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5859","DOI":"10.1039\/D3BM00305A","article-title":"Delivery of Gold Nanoparticle-Conjugated M2e Influenza Vaccine in Mice Using Coated Microneedles","volume":"11","author":"Nesovic","year":"2023","journal-title":"Biomater. Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"105","DOI":"10.3390\/vaccines3010105","article-title":"M2e-Based Universal Influenza A Vaccines","volume":"3","author":"Deng","year":"2015","journal-title":"Vaccines"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D624","DOI":"10.1093\/nar\/gkx1134","article-title":"The MEROPS Database of Proteolytic Enzymes, Their Substrates and Inhibitors in 2017 and a Comparison with Peptidases in the PANTHER Database","volume":"46","author":"Rawlings","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_58","unstructured":"Ziegler, I., Ma, B., Nie, E., Bischl, B., R\u00fcgamer, D., Schubert, B., and Dorigatti, E. (2022). What Cleaves? Is Proteasomal Cleavage Prediction Reaching a Ceiling?. arXiv."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1002\/pro.3113","article-title":"PACMANS: A Bioinformatically Informed Algorithm to Predict, Design, and Disrupt Protease-on-Protease Hydrolysis","volume":"26","author":"Barry","year":"2017","journal-title":"Protein Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4076","DOI":"10.1021\/am3028537","article-title":"Stable Conjugates of Peptides with Gold Nanorods for Biomedical Applications with Reduced Effects on Cell Viability","volume":"5","author":"Adura","year":"2013","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2202","DOI":"10.1021\/acsomega.7b01700","article-title":"Manipulation of the Geometry and Modulation of the Optical Response of Surfactant-Free Gold Nanostars: A Systematic Bottom-Up Synthesis","volume":"3","author":"Johnson","year":"2018","journal-title":"ACS Omega"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 Years of Image Analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:16:19Z","timestamp":1790136979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/18\/8400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,21]]},"references-count":62,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27188400"],"URL":"https:\/\/doi.org\/10.3390\/ijms27188400","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,21]]}}}