{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T22:25:36Z","timestamp":1787610336880,"version":"build-2736575974"},"reference-count":47,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Torino (Bando Finanziamenti alla Ricerca di Ateneo ex 60%)","award":["#20227YTZE3"],"award-info":[{"award-number":["#20227YTZE3"]}]},{"name":"Italian Ministry for University and Research (MUR)","award":["#20227YTZE3"],"award-info":[{"award-number":["#20227YTZE3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide due to its resistance to conventional therapies that is attributed to its dense and acidic tumor microenvironment. Chemotherapy based on gemcitabine usually lacks efficacy due to poor drug penetration and the metabolic characteristics of the cells adapted to grow at a more acidic pHe, thus presenting a more aggressive phenotype. In this context, photodynamic therapy (PDT) offers a promising alternative since it generally does not suffer from the same patterns of cross-resistance observed with chemotherapy drugs. In the present work, a novel bromine-substituted heptamethine-cyanine dye (BrCY7) was synthesized, loaded into PEG-PLGA NPs, and tested on the pancreatic ductal adenocarcinoma cell line cultured under physiological (PANC-1 CT) and acidic (PANC-1 pH selected) conditions, which promotes the selection of a more aggressive phenotype. The cytotoxicity of BrCY7-PEG-PLGA is dose-dependent, with an IC50 of 2.15 \u00b5M in PANC-1 CT and 2.87 \u00b5M in PANC-1 pH selected. Notably, BrCY7-PEG-PLGA demonstrated a phototoxic effect against PANC-1 pH selected cells but not on PANC-1 CT, which makes these findings particularly relevant since PANC-1 pH selected cells are more resistant to gemcitabine as compared with PANC-1 CT cells.<\/jats:p>","DOI":"10.3390\/polym17081101","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T08:24:07Z","timestamp":1744964647000},"page":"1101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["NIR pH-Responsive PEGylated PLGA Nanoparticles as Effective Phototoxic Agents in Resistant PDAC Cells"],"prefix":"10.3390","volume":"17","author":[{"given":"Degnet Melese","family":"Dereje","sequence":"first","affiliation":[{"name":"NIS Interdepartmental and INSTM Reference Centre, Department of Chemistry, University of Torino, Via G. Quarello 15A, 10135 Torino, Italy"},{"name":"Bahir Dar Institute of Technology, Department of Chemical Engineering, Bahir Dar University, Polypeda 01, Bahir Dar 0026, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bianco","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy"},{"name":"Department of Chemistry, Biology and Biotechnology, University of Perugia, Via dell\u2019 Elce di Sotto 8, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Pontremoli","sequence":"additional","affiliation":[{"name":"NIS Interdepartmental and INSTM Reference Centre, Department of Chemistry, University of Torino, Via G. Quarello 15A, 10135 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4576-1594","authenticated-orcid":false,"given":"Alessandra","family":"Fiorio Pla","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6421-3492","authenticated-orcid":false,"given":"Nadia","family":"Barbero","sequence":"additional","affiliation":[{"name":"NIS Interdepartmental and INSTM Reference Centre, Department of Chemistry, University of Torino, Via G. Quarello 15A, 10135 Torino, Italy"},{"name":"Institute of Science and Technology for Ceramics (ISSMC-CNR), Via Granarolo, 64, 48018 Faenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mercanti, L., Sindaco, M., Mazzone, M., Di Marcantonio, M.C., Piscione, M., Muraro, R., and Mincione, G. (2023). PDAC, the Influencer Cancer: Cross-Talk with Tumor Microenvironment and Connected Potential Therapy Strategies. Cancers, 15.","DOI":"10.3390\/cancers15112923"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nrc3110","article-title":"Dysregulated PH: A Perfect Storm for Cancer Progression","volume":"11","author":"Webb","year":"2011","journal-title":"Nat. Rev. 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