{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T02:06:55Z","timestamp":1778119615310,"version":"3.51.4"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\/MCTES, Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia and Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior","award":["UIDB\/50006\/2020|UIDP\/50006\/2020"],"award-info":[{"award-number":["UIDB\/50006\/2020|UIDP\/50006\/2020"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Understanding how nanoparticles\u2019 properties influence their cellular interactions is a bottleneck for improving the design of carriers. Macrophage polarization governs their active role in solving infections or tissue repair. To unravel the effect of carbohydrate-targeting mannose receptors on the macrophage surface, drug-free fucoidan\/chitosan nanoparticles were functionalized using mannose (M) and mannan (Mn). Polyelectrolyte complex nanoparticles were obtained upon chitosan self-assembly using fucoidan. The functionalized nanoparticles were characterized in terms of their physicochemical characteristics, chemical profile, and carbohydrate orientation. The nanoparticles varied in size from 200 to 400 nm, were monodisperse, and had a stable negative zeta potential with a low aggregation tendency. The nonfunctionalized and functionalized nanoparticles retained their properties for up to 12 weeks. Cell viability and internalization studies were performed for all the designed nanoparticles in the THP-1 monocytes and THP-1-differentiated macrophages. The expression of the mannose receptor was verified in both immune cells. The carbohydrate-functionalized nanoparticles led to their activation and the production of pro-inflammatory cytokines interleukin (IL)-1\u03b2, IL-6, and tumour necrosis factor (TNF)-\u03b1. Both M- and Mn-coated nanoparticles modulate macrophages toward an M1-polarized state. These findings demonstrate the tailoring of these nanoplatforms to interact and alter the macrophage phenotype in vitro and represent their therapeutic potential either alone or in combination with a loaded drug for future studies.<\/jats:p>","DOI":"10.3390\/ijms24129908","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:59:57Z","timestamp":1686279597000},"page":"9908","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting the Mannose Receptor with Functionalized Fucoidan\/Chitosan Nanoparticles Triggers the Classical Activation of Macrophages"],"prefix":"10.3390","volume":"24","author":[{"given":"Filipa","family":"Serrasqueiro","sequence":"first","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-3187","authenticated-orcid":false,"given":"Ana Isabel","family":"Barbosa","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8777-5877","authenticated-orcid":false,"given":"Sofia A. Costa","family":"Lima","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Instituto de Ci\u00eancias Biom\u00e9dicas de Abel Salazar, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0736-2835","authenticated-orcid":false,"given":"Salette","family":"Reis","sequence":"additional","affiliation":[{"name":"LAQV, REQUIMTE, Departamento de Ci\u00eancias Qu\u00edmicas, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","unstructured":"Bhat, K.H. (2019). Macrophages: The Potent Immunoregulatory Innate Immune Cells. Macrophage Activation\u2014Biology and Disease, IntechOpen."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: In vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.1182\/blood-2009-07-231795","article-title":"Orchestration of macrophage polarization","volume":"114","author":"Mantovani","year":"2009","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Andrade, R.G., Reis, B., Costas, B., Lima, S.A., and Reis, S. (2021). Modulation of Macrophages M1\/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles. Polymers, 13.","DOI":"10.3390\/polym13010088"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1600-065X.2009.00789.x","article-title":"Mannose-binding lectin and innate immunity","volume":"230","author":"Takahashi","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ejps.2012.12.006","article-title":"A review of current nanoparticle and targeting moieties for the delivery of cancer therapeutics","volume":"48","author":"Steichen","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4762","DOI":"10.1016\/j.biomaterials.2012.03.027","article-title":"Tailoring the immune response by targeting C-type lectin receptors on alveolar macrophages using \u201cpathogen-like\u201d amphiphilic polyanhydride nanoparticles","volume":"33","author":"Roychoudhury","year":"2012","journal-title":"Biomaterials"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"387","DOI":"10.2217\/nnm.14.116","article-title":"Surface functionalization of polymeric nanospheres modulates macrophage activation: Relevance in leishmaniasis therapy","volume":"10","author":"Barros","year":"2015","journal-title":"Nanomedicine"},{"key":"ref_9","first-page":"197","article-title":"Mannose-decorated hybrid nanoparticles for enhanced macrophage targeting","volume":"17","author":"Hatami","year":"2019","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1007\/s13346-021-01003-7","article-title":"Mannose-conjugated chitosan nanoparticles for delivery of Rifampicin to Osteoarticular tuberculosis","volume":"11","author":"Prabhu","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_11","first-page":"3670","article-title":"Newman, Natural products: A continuing source of novel drug leads","volume":"1830","author":"Cragg","year":"2013","journal-title":"BBA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Barbosa, A.I., Coutinho, A.J., Costa Lima, S.A., and Reis, S. (2019). Marine Polysaccharides in Pharmaceutical Applications: Fucoidan and Chitosan as Key Players in the Drug Delivery Match Field. Mar. Drugs, 17.","DOI":"10.3390\/md17120654"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Barbosa, A.I., Costa Lima, S.A., and Reis, S. (2019). Application of pH-Responsive Fucoidan\/Chitosan Nanoparticles to Improve Oral Quercetin Delivery. Molecules, 24.","DOI":"10.3390\/molecules24020346"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ijbiomac.2020.04.233","article-title":"Mucoadhesive and pH responsive fucoidan-chitosan nanoparticles for the oral delivery of methotrexate","volume":"158","author":"Coutinho","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ijbiomac.2018.12.014","article-title":"Development of methotrexate loaded fucoidan\/chitosan nanoparticles with anti-inflammatory potential and enhanced skin permeation","volume":"124","author":"Barbosa","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.2217\/nnm-2017-0055","article-title":"Development of genipin-crosslinked fucoidan\/chitosan-N-arginine nanogels for preventing Helicobacter infection","volume":"12","author":"Lin","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"120548","DOI":"10.1016\/j.ijpharm.2021.120548","article-title":"Fucoidan\/chitosan nanoparticles functionalized with anti-ErbB-2 target breast cancer cells and impair tumor growth in vivo","volume":"600","author":"Oliveira","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2007.08.001","article-title":"Nanoparticles for drug delivery: The need for precision in reporting particle size parameters","volume":"69","author":"Gaumet","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_19","first-page":"1000003","article-title":"Exploitation of the Macrophage Mannose Receptor (CD206) in Infectious Disease Diagnostics and Therapeutics","volume":"1","author":"Azad","year":"2014","journal-title":"J. Cytol. Mol. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1189\/jlb.0512231","article-title":"The mannose receptor","volume":"92","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1021\/bm101482r","article-title":"Surface charge affects cellular uptake and intracellular traffcking of chitosan-based nanoparticles","volume":"12","author":"Yue","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8902","DOI":"10.1016\/j.actbio.2013.06.024","article-title":"Functionalization of polyanhydride microparticles with di-mannose influences uptake by and intracellular fate within dendritic cells","volume":"9","author":"Phanse","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.jconrel.2021.10.017","article-title":"Amphiphilic galactomannan nanoparticles trigger the alternative activation of murine macrophages","volume":"339","author":"Peled","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1021\/mp200213r","article-title":"Mannose-functionalized \u201cpathogen-like\u201d polyanhydride nanoparticles target C-type lectin receptors on dendritic cells","volume":"8","author":"Song","year":"2011","journal-title":"Mol. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.1002\/jbm.a.36128","article-title":"Functionalization promotes pathogen-mimicking characteristics of polyanhydride nanoparticle adjuvants","volume":"105","author":"Phanse","year":"2017","journal-title":"J. Biomed. Mater. Res. 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