{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:36:08Z","timestamp":1776872168777,"version":"3.51.2"},"reference-count":45,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Research Council, Consolidator Grant Magtendon","award":["772817"],"award-info":[{"award-number":["772817"]}]},{"name":"European Research Council, Consolidator Grant Magtendon","award":["SFRD\/BD\/144816\/2019"],"award-info":[{"award-number":["SFRD\/BD\/144816\/2019"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["772817"],"award-info":[{"award-number":["772817"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["SFRD\/BD\/144816\/2019"],"award-info":[{"award-number":["SFRD\/BD\/144816\/2019"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the Scientific Employment Stimulus\u2014Individual Call: 2020.01157.CEECIND","award":["772817"],"award-info":[{"award-number":["772817"]}]},{"name":"FCT-Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia under the Scientific Employment Stimulus\u2014Individual Call: 2020.01157.CEECIND","award":["SFRD\/BD\/144816\/2019"],"award-info":[{"award-number":["SFRD\/BD\/144816\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The persistence of inflammatory mediators in tissue niches significantly impacts regenerative outcomes and contributes to chronic diseases. Interleukin-4 (IL4) boosts pro-healing phenotypes in macrophages (M\u03c6) and triggers the activation of signal transducer and activator of transcription 6 (STAT6). Since the IL4\/STAT6 pathway reduces M\u03c6 responsiveness to inflammation in a targeted and precise manner, IL4 delivery offers personalized possibilities to overcome inflammatory events. Despite its therapeutic potential, the limited success of IL4-targeted delivery is hampered by inefficient vehicles. Magnetically assisted technologies offer precise and tunable nanodevices for the delivery of cytokines by combining contactless modulation, high tissue penetration, imaging features, and low interference with the biological environment. Although superparamagnetic iron oxide nanoparticles (SPION) have shown clinical applicability in imaging, SPION-based approaches have rarely been explored for targeted delivery and cell programming. Herein, we hypothesized that SPION-based carriers assist in efficient IL4 delivery to M\u03c6, favoring a pro-regenerative phenotype (M2\u03c6). Our results confirmed the efficiency of SPION-IL4 and M\u03c6 responsiveness to SPION-IL4 with evidence of STAT6-mediated polarization. SPION-IL4-treated M\u03c6 showed increased expression of M2\u03c6 associated-mediators (IL10, ARG1, CCL2, IL1Ra) when compared to the well-established soluble IL4. The ability of SPION-IL4 to direct M\u03c6 polarization using sophisticated magnetic nanotools is valuable for resolving inflammation and assisting innovative strategies for chronic inflammatory conditions.<\/jats:p>","DOI":"10.3390\/ijms232315125","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T01:44:46Z","timestamp":1669945486000},"page":"15125","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Controlling Macrophage Polarization to Modulate Inflammatory Cues Using Immune-Switch Nanoparticles"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6663-6851","authenticated-orcid":false,"given":"Ana F.","family":"Almeida","sequence":"first","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-8890","authenticated-orcid":false,"given":"Margarida S.","family":"Miranda","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"given":"Adriana","family":"Vinhas","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-9292","authenticated-orcid":false,"given":"Ana I.","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2036-6291","authenticated-orcid":false,"given":"Manuela E.","family":"Gomes","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4483-5689","authenticated-orcid":false,"given":"M\u00e1rcia T.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"3B\u2019s Research Group, I3Bs\u2013Research Institute on Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de Ci\u00eancia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimar\u00e3es, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, 4710-057 Braga\/Guimar\u00e3es, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"376","DOI":"10.31635\/ccschem.020.202000165","article-title":"Recent Progress in Capturing and Neutralizing Inflammatory Cytokines","volume":"2","author":"Zhang","year":"2020","journal-title":"CCS Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41584-018-0109-2","article-title":"Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis","volume":"15","author":"Chen","year":"2019","journal-title":"Nat. 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