Study of the combination of self-activating photodynamic therapy and chemotherapy for cancer treatment

Cancer is a very challenging disease to treat, both in terms of treatment eficiency and side-effects. 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.This research was co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER through COMPETE-POFC, grant number PTDC/QEQ-QFI/0289/2014; funded by FEDER through COMPETE2020, grant POCI-01-0145-FEDER-006980; funded by FEDER through NORTE2020, grant number NORTE-01-0145-FEDER 000028; co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER through COMEPETE2020-POCI, grant number POCI-01-0145-FEDER-007274; co-funded by Fundação para a Ciência e Tecnologia (FCT) and FEDER, grant number IF/00092/2014/CP1255/CT0004; funded by Fundação para a Ciência e Tecnologia (FCT), grant number SFRH/BD/140734/2018; funded by Fundação para a Ciência e Tecnologia (FCT), grant number UID/QUI/50006/2013; funded by Fundação para a Ciência e Tecnologia (FCT), grant number PTDC/BIA-MIA/29059/2017; funded by Fundação para a Ciência e Tecnologia (FCT), grant number CEECIND/01425/2017; funded by Fundação para a Ciência e Tecnologia (FCT), grant number SFRH/BD/143211/2019