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While providing essential protection against pathogens, BBB also poses a major challenge by restricting the delivery of systemically administered therapeutics. Consequently, there is a pressing need for innovative strategies that can efficiently and selectively target neuronal populations to treat diverse brain disorders. Nanomaterials enable transcellular transport across the endothelial layer; however, given the biomolecular corona paradigm, designing biomimetic hybrid nanoconstructs that preserve and leverage biological functionality within a complex physiological environment is more promising. Here, we investigated the potential of M13 bacteriophages as biocompatible and versatile nanovectors across the BBB. M13 phages exhibited: (\n                    <jats:italic>i<\/jats:italic>\n                    ) a high cargo capacity within the main protein capsomer (here exploited for fluorescent labeling); (\n                    <jats:italic>ii<\/jats:italic>\n                    ) offered genetic flexibility for ligand display; (\n                    <jats:italic>iii<\/jats:italic>\n                    ) showed a natural propensity to efficiently cross the endothelial layer via specific intracellular pathways; (\n                    <jats:italic>iv<\/jats:italic>\n                    ) maintained their structure and functionality intact. We also demonstrate that M13 phages engineered to target specific neuronal populations via single\u2010domain antibody display retain their specificity after BBB translocation and in a protein\u2010 and cell\u2010crowded environment. Overall, our results provide mechanistic insights emphasizing an unprecedented field of application for (engineered) M13 phages as biomimetic nanotools for targeting and delivery across the BBB.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202600029","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T05:11:47Z","timestamp":1780117907000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Blood\u2010Brain Barrier Crossing by Biomimetic M13 Phage Vectors for Targeted Neuronal Delivery"],"prefix":"10.1002","volume":"15","author":[{"given":"Silvia","family":"Vercellino","sequence":"first","affiliation":[{"name":"Center for Synaptic Neuroscience and Technology Istituto Italiano di Tecnologia  Genova Italy"},{"name":"IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3740-007X","authenticated-orcid":false,"given":"Lucia","family":"Pappagallo","sequence":"additional","affiliation":[{"name":"Center for Synaptic Neuroscience and Technology Istituto Italiano di Tecnologia  Genova Italy"},{"name":"Dipartimento di Farmacia e Biotecnologie Alma Mater Studiorum \u2013 Universit\u00e0 di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"De Chirico","sequence":"additional","affiliation":[{"name":"Fondazione Pisana per la Scienza ONLUS  San Giuliano Terme Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2732-5484","authenticated-orcid":false,"given":"Luca","family":"Boselli","sequence":"additional","affiliation":[{"name":"Nanobiointeractions &amp; Nanodiagnostics Istituto Italiano di Tecnologia (IIT)  Genova Italy"},{"name":"Dipartimento di Promozione delle Scienze Umane e della Qualit\u00e0 della Vita Universit\u00e0 Telematica San Raffaele Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0034-2978","authenticated-orcid":false,"given":"Hazem","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Center for Synaptic Neuroscience and Technology Istituto Italiano di Tecnologia  Genova Italy"},{"name":"Nanobiointeractions &amp; Nanodiagnostics Istituto Italiano di Tecnologia (IIT)  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Spagnoletti","sequence":"additional","affiliation":[{"name":"Center for Synaptic Neuroscience and Technology Istituto Italiano di Tecnologia  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Pittaluga","sequence":"additional","affiliation":[{"name":"Center for Synaptic Neuroscience and Technology Istituto Italiano di Tecnologia  Genova Italy"},{"name":"IRCCS Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1597-6404","authenticated-orcid":false,"given":"Paolo Emidio","family":"Costantini","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia e Biotecnologie Alma Mater Studiorum \u2013 Universit\u00e0 di Bologna  Bologna Italy"},{"name":"IRCCS AOUBO Sant'Orsola \u2013 Laboratory of Preclinical and Translational Research in Oncology (PRO)  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9583-2146","authenticated-orcid":false,"given":"Matteo","family":"Calvaresi","sequence":"additional","affiliation":[{"name":"IRCCS AOUBO Sant'Orsola \u2013 Laboratory of Preclinical and Translational Research in Oncology (PRO)  Bologna Italy"},{"name":"Dipartimento di Chimica \u201cGiacomo Ciamician\u201d Alma Mater Studiorum \u2013 Universit\u00e0 di Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-0612","authenticated-orcid":false,"given":"Pier Paolo","family":"Pompa","sequence":"additional","affiliation":[{"name":"Nanobiointeractions &amp; Nanodiagnostics Istituto Italiano di Tecnologia (IIT)  Genova Italy"},{"name":"College of Optical Science and Engineering Zhejiang University  Hangzhou P. 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