Cancer is a very challenging disease to treat, both in terms of treatment efficiency 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.