{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T05:15:35Z","timestamp":1783574135456,"version":"3.55.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bladder cancer remains a highly recurrent malignancy with limited long-term response to conventional therapies. The development of new treatments is also hindered by the lack of preclinical models that accurately reproduce human disease. In this context, Oncopig-derived models provide a translationally relevant platform for evaluating candidate therapies before progression to\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we performed a preclinical\n                      <jats:italic>in vitro<\/jats:italic>\n                      screening of three palladium(II)-porphyrins, 3-Pd(PPh\n                      <jats:sub>3<\/jats:sub>\n                      ), 3-Pd(dppf), and 3-Pd(PEPSI), in human (T24, RT4, 5637) and Oncopig-derived bladder cancer cell models. Cytotoxicity was assessed under light and dark conditions using MTT and LIVE\/DEAD assays, while intracellular ROS generation was quantified via DCFH-DA fluorescence. Gene expression profiling (qRT-PCR) targeted oxidative stress and apoptosis markers (SOD, CAT, GPx, BAX, BCL2, CASP3\/8\/9), and nuclear morphology was analyzed using DAPI staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      All three compounds exhibited light-dependent cytotoxicity with minimal dark toxicity. While 3-Pd(PPh\n                      <jats:sub>3<\/jats:sub>\n                      ) and 3-Pd(dppf) demonstrated potent photodynamic activity with nanomolar IC\n                      <jats:sub>50<\/jats:sub>\n                      values, 3-Pd(PEPSI) showed consistently higher IC\n                      <jats:sub>50<\/jats:sub>\n                      values across the tested bladder cancer cell lines, indicating lower photodynamic potency under the evaluated conditions. Photoactivation triggered significant ROS production and upregulation of CAT and CASP3, alongside increased BAX\/BCL2 ratios, supporting a ROS-mediated apoptotic mechanism. Notably, Oncopig-derived cells exhibited molecular and phenotypic responses closely matching those of human bladder cancer cell lines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings support the translational potential of Pd(II)-porphyrins for bladder cancer PDT and position Oncopig-derived\n                      <jats:italic>in vitro<\/jats:italic>\n                      models as a responsible preclinical screening layer to prioritize photosensitizers before future large-animal validation of localized and image-guided PDT strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1882402","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:51Z","timestamp":1783571031000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Preclinical translational screening of palladium(II)-porphyrin photosensitizers across human and Oncopig bladder cancer cell lines"],"prefix":"10.3389","volume":"16","author":[{"given":"Valentina G.","family":"Ferreira","sequence":"first","affiliation":[{"name":"Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Technological Development Center, Federal University of Pelotas","place":["Pelotas, Brazil"]},{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eduarda","family":"Ehlert","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Technological Development Center, Federal University of Pelotas","place":["Pelotas, Brazil"]},{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna S.","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Technological Development Center, Federal University of Pelotas","place":["Pelotas, Brazil"]},{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda S. S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Technological Development Center, Federal University of Pelotas","place":["Pelotas, Brazil"]},{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isadora","family":"Tisoco","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Santa Maria","place":["Santa Maria, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Dam\u00e9","family":"Sim\u00f5es","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Technological Development Center, Federal University of Pelotas","place":["Pelotas, Brazil"]},{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo A.","family":"Iglesias","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Santa Catarina","place":["Florian\u00f3polis, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia \u00d3.","family":"Pessoa","sequence":"additional","affiliation":[{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]},{"name":"Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Cear\u00e1","place":["Fortaleza, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana K.","family":"Seixas","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Oncology Research Group, Cancer Biotechnology Laboratory, Technological Development Center, Federal University of Pelotas","place":["Pelotas, Brazil"]},{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Lucia Z.","family":"Dagli","sequence":"additional","affiliation":[{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]},{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, SP, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie A.","family":"Rund","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences, University of Illinois","place":["Urbana, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle M.","family":"Schachtschneider","sequence":"additional","affiliation":[{"name":"INCT T-Bio2: Translational Biodiscovery and Biomodels","place":["Pelotas, Rio Grande do Sul, Brazil"]},{"name":"Sus Clinicals 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