{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:08:04Z","timestamp":1782310084018,"version":"3.54.5"},"reference-count":73,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005357","name":"Slovak Research and Development Agency","doi-asserted-by":"publisher","award":["APVV-20-0129"],"award-info":[{"award-number":["APVV-20-0129"]}],"id":[{"id":"10.13039\/501100005357","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Ministry of Education, Research, Development and Youth of the Slovak Republic","award":["VEGA 2\/0081\/25"],"award-info":[{"award-number":["VEGA 2\/0081\/25"]}]},{"name":"The EU NextGenerationEU through the Recovery and Resilience Plan for Slovakia","award":["BCOrgFluorIDA No. 09I03-03-V04-00007"],"award-info":[{"award-number":["BCOrgFluorIDA No. 09I03-03-V04-00007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The increasing prevalence of multidrug-resistant bacteria necessitates alternative therapeutic strategies that combine antimicrobial efficacy with immunomodulatory properties. Here, we report the immunostimulatory activity and antibacterial potential of the amino-functionalized metal\u2013organic framework MIL-101(Al)-NH2 as a carrier for penicillin (PEN) and hypericin (Hyp), a photodynamically active compound. Structural and physicochemical characterization confirmed successful encapsulation of PEN, Hyp, and their combination within MIL-101(Al)-NH2, with distinct effects on porosity, release kinetics, and thermal stability. Drug release studies revealed rapid Hyp liberation triggered by serum components, whereas PEN exhibited a biphasic, diffusion-controlled profile. Using a quail chorioallantoic membrane (CAM) model, we demonstrated that MIL-101(Al)-NH2 enhances interferon-\u03b1 expression, indicating intrinsic immunostimulatory activity, and that Hyp-loaded systems promote angiogenic responses. In a bacterial infection CAM model, MIL-101(Al)-NH2 carriers loaded with Hyp or Hyp\/PEN induced immunomodulatory changes and, upon photodynamic activation, inhibited bacterial growth. While Gram-negative Escherichia coli remained resistant, Gram-positive Staphylococcus epidermidis was effectively suppressed by photodynamic therapy (PDT), and Hyp\/PEN co-delivery overcame bacterial resistance to PEN. These results highlight MIL-101(Al)-NH2 as a multifunctional nanoplatform with immunostimulatory capacity and PDT-enhanced antibacterial activity, offering a promising strategy to combat antibiotic resistance and infections associated with medical implants.<\/jats:p>","DOI":"10.3390\/ijms262311681","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:03:13Z","timestamp":1764687793000},"page":"11681","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Immunostimulatory Effect of MIL-101(Al)-NH2 In Vivo and Its Potential to Overcome Bacterial Resistance to Penicillin Enhanced by Hypericin-Induced Photodynamic Therapy"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-6001","authenticated-orcid":false,"given":"Mariana","family":"M\u00e1\u010dajov\u00e1","sequence":"first","affiliation":[{"name":"Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 Cesta 9, SK-840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4398-1665","authenticated-orcid":false,"given":"\u013dubo\u0161","family":"Ambro","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Biosciences, Technology and Innovation Park, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Jesenn\u00e1 5, SK-041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majlinda","family":"Meta","sequence":"additional","affiliation":[{"name":"Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 Cesta 9, SK-840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u013dubo\u0161","family":"Zau\u0161ka","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Science, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Moyzesova 11, SK-041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ter\u00e9zia","family":"Guly\u00e1sov\u00e1","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Biosciences, Technology and Innovation Park, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Jesenn\u00e1 5, SK-041 54 Ko\u0161ice, Slovakia"},{"name":"Department of Biophysics, Faculty of Science, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Jesenn\u00e1 5, SK-041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9933-5147","authenticated-orcid":false,"given":"Boris","family":"Bil\u010d\u00edk","sequence":"additional","affiliation":[{"name":"Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 Cesta 9, SK-840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"\u010cavarga","sequence":"additional","affiliation":[{"name":"Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 Cesta 9, SK-840 05 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7664-8802","authenticated-orcid":false,"given":"Gabriela","family":"Zelenkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Ostrava, 30, Dubna 22, CZ-701 03 Ostrava, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1290-5774","authenticated-orcid":false,"given":"Erik","family":"Sedl\u00e1k","sequence":"additional","affiliation":[{"name":"Center for Interdisciplinary Biosciences, Technology and Innovation Park, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Jesenn\u00e1 5, SK-041 54 Ko\u0161ice, Slovakia"},{"name":"Department of Biochemistry, Faculty of Science, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Moyzesova 11, SK-041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6044-6683","authenticated-orcid":false,"given":"Miroslav","family":"Alm\u00e1\u0161i","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Science, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Moyzesova 11, SK-041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0042-2097","authenticated-orcid":false,"given":"Veronika","family":"Hunto\u0161ov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Animal Biochemistry and Genetics, Centre of Biosciences, Slovak Academy of Sciences, D\u00fabravsk\u00e1 Cesta 9, SK-840 05 Bratislava, Slovakia"},{"name":"Center for Interdisciplinary Biosciences, Technology and Innovation Park, Pavol Jozef \u0160af\u00e1rik University in Ko\u0161ice, Jesenn\u00e1 5, SK-041 54 Ko\u0161ice, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mandla, S., Davenport Huyer, L., and Radisic, M. 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