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To overcome these problems, there have been extensive studies regarding the possibility of improving treatment by employing combination therapy, and by exploring therapeutic modalities with reduced side-effects (such as photodynamic therapy (PDT)). Herein, this work has two aims: (i) to develop self-activating photosensitizers for use in light-free photodynamic therapy, which would eliminate light-related restrictions that this therapy currently possesses; (ii) to assess their co-treatment potential when combined with reference chemotherapeutic agents (Tamoxifen and Metformin). We synthesized three new photosensitizers capable of self-activation and singlet oxygen production via a chemiluminescent reaction involving only a cancer marker and without requiring a light source. Cytotoxicity assays demonstrated the cytotoxic activity of all photosensitizers for prostate and breast tumor cell lines. Analysis of co-treatment effects revealed significant improvements for breast cancer, producing better results for all combinations than just for the individual photosensitizers and even Tamoxifen. By its turn, co-treatment for prostate cancer only presented better results for one combination than for just the isolated photosensitizers and Metformin. Nevertheless, it should be noted that the cytotoxicity of the isolated photosensitizers in prostate tumor cells was already very appreciable.<\/jats:p>","DOI":"10.3390\/biom9080384","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T11:19:06Z","timestamp":1566386346000},"page":"384","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Study of the Combination of Self-Activating Photodynamic Therapy and Chemotherapy for Cancer Treatment"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5647-8455","authenticated-orcid":false,"given":"Lu\u00eds","family":"Pinto da Silva","sequence":"first","affiliation":[{"name":"Chemistry Research Unit (CIQUP), Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"},{"name":"LACOMEPHI, GreenUPorto, Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"}]},{"given":"Carla M.","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Chemistry Research Unit (CIQUP), Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1666-3514","authenticated-orcid":false,"given":"Ara","family":"N\u00fa\u00f1ez-Montenegro","sequence":"additional","affiliation":[{"name":"Chemistry Research Unit (CIQUP), Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"}]},{"given":"Paulo J.O.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Chemistry Research Unit (CIQUP), Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1420-5042","authenticated-orcid":false,"given":"Diana","family":"Duarte","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"I3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"}]},{"given":"Jos\u00e9 E.","family":"Rodr\u00edguez-Borges","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, 4169-007 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"},{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua J\u00falio Amaral de Carvalho 45, 4200-135 Porto, Portugal"},{"name":"I3S, Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal"},{"name":"Department of Molecular Pathology and Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8478-3441","authenticated-orcid":false,"given":"Joaquim C.G.","family":"Esteves da Silva","sequence":"additional","affiliation":[{"name":"Chemistry Research Unit (CIQUP), Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"},{"name":"LACOMEPHI, GreenUPorto, Faculty of Sciences of University of Porto (FCUP), Rua do Campo Alegre 687, 4169-007 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,20]]},"reference":[{"key":"ref_1","unstructured":"Cancer Research UK (2019, July 08). 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