{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:09:56Z","timestamp":1771240196815,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Research through the PNRR. project SEELIFE","award":["M4\/C2\/L3.1.1)"],"award-info":[{"award-number":["M4\/C2\/L3.1.1)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Photodynamic therapy (PDT) is a technique based on the use of photosensitizers activated by light to destroy cancer cells in the presence of oxygen. This enables localized cancer treatment and, in some settings, fluorescence-guided visualization. However, the efficacy and clinical translation of PDT have been limited by the low specificity of traditional photosensitizers. The aim of the study is to create a ligand-guided PDT approach for pancreatic ductal adenocarcinoma (PDAC) using a peptide-conjugated photosensitizer binding to integrin \u03b1v\u03b26, which is a receptor linked to tumor growth and prevalent in PDAC cells. Current treatment options for this tumor are limited, with surgical resection and chemotherapy only effective when the tumor is detected early. Given the limited treatment options for PDAC, PDT via \u03b1v\u03b26 offers a new pathway for precision treatment. The cyclic peptide cyclo[FRGDLAFp(NMe)K], recognized for its high affinity to \u03b1v\u03b26, was chosen to guide a phthalocyanine-class photosensitizer toward \u03b1v\u03b26-expressing PDAC models. The PDT approach was further refined by developing 3D spheroid models and in vivo BxPc3 xenograft models in NOD\/SCID mice, where its therapeutic efficacy was assessed. In the absence of a non-targeted control photosensitizer, a contribution from non-specific accumulation and EPR effects in the in vivo setting cannot be fully ruled out. This study highlights the potential of a peptide-guided photosensitizer, demonstrating uptake and photodynamic activity in spheroids, with moderate in vivo results addressing tumor microenvironment challenges. Optimization of PDT dosing, laser precision, and preclinical models, such as patient-derived xenografts, are crucial to enhance clinical translation.<\/jats:p>","DOI":"10.3390\/ijms27041838","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"1838","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptide-Guided Photodynamic Therapy via Integrin \u03b1v\u03b26 in Pancreatic Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3804-5031","authenticated-orcid":false,"given":"Miriam","family":"Roberto","sequence":"first","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular & Preclinical Imaging Centers, University of Torino, 10125 Torino, Italy"},{"name":"Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7722-557X","authenticated-orcid":false,"given":"Francesca","family":"La Cava","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3644-0609","authenticated-orcid":false,"given":"Francesca","family":"Arena","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Cordaro","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2643-8851","authenticated-orcid":false,"given":"Francesco","family":"Stummo","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7330-6498","authenticated-orcid":false,"given":"Claudia","family":"Cabella","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8556-8556","authenticated-orcid":false,"given":"Rachele","family":"Stefania","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation, University of Eastern Piedmont \u201cAmedeo Avogadro\u201d, 15121 Alessandria, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2589-216X","authenticated-orcid":false,"given":"Luca D.","family":"D\u2019Andrea","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences and Technologies \u2018G. Natta\u2019, CNR, 20131 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6616-8418","authenticated-orcid":false,"given":"Francesco","family":"Blasi","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3800-566X","authenticated-orcid":false,"given":"Enzo","family":"Terreno","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular & Preclinical Imaging Centers, University of Torino, 10125 Torino, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0038-4768","authenticated-orcid":false,"given":"Erika","family":"Reitano","sequence":"additional","affiliation":[{"name":"Bracco Research Centre, Bracco Imaging Spa, Via Ribes 5, 10010 Colleretto Giacosa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1056\/NEJMra1404198","article-title":"Pancreatic adenocarcinoma","volume":"371","author":"Ryan","year":"2014","journal-title":"N. 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