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However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and\/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony\u2010forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The improvement can be related to the synergistic effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG NPs. Functionalized NPs with anti\u2010F4\/80 and anti\u2010MARCO antibodies, or mannose without PEG and treated with PC, show an improved uptake but, in the presence of PEG, significantly reduce the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution.<\/jats:p>","DOI":"10.1002\/mabi.202300197","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T15:14:46Z","timestamp":1693235686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of Protein Corona on the Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1371-4056","authenticated-orcid":false,"given":"Susana P.","family":"Mej\u00eda","sequence":"first","affiliation":[{"name":"Max Planck Tandem Group in Nanobioengineering Institute of Chemistry Faculty of Natural and Exact Sciences University of Antioquia  Complejo Ruta N, Calle 67 No 52\u201020 Medellin 050010 Colombia"},{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard da Costa","family":"Marques","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Landfester","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6249-8092","authenticated-orcid":false,"given":"Jahir","family":"Orozco","sequence":"additional","affiliation":[{"name":"Max Planck Tandem Group in Nanobioengineering Institute of Chemistry Faculty of Natural and Exact Sciences University of Antioquia  Complejo Ruta N, Calle 67 No 52\u201020 Medellin 050010 Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Mail\u00e4nder","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Polymer Research  55128 Mainz Germany"},{"name":"Dermatology Clinic University Medical Center of the Johannes Gutenberg University Mainz  Langenbeck str. 1 55131 Mainz Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,10]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.61.080706.093305"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0190-9622(96)80121-6"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-842X(98)01431-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13389"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00225"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25163760"},{"key":"e_1_2_9_7_1","first-page":"27","volume-title":"Practical Pharmacology for the Pharmacy Technician","author":"Sakai J. 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