Some types of cancer, such as triple-negative breast cancer, have a poor prognosis when treated with systemic chemotherapy. Photodynamic therapy (PDT) is an alternative to systemic chemotherapy that uses a photosensitizing compound (PS) that is taken up by cells and produces reactive oxygen species when exposed to specific wavelengths of light. While the PS can be administered either systemically for internal tumors or topically for surface tumors, targeting of cells in a specific tissue is achieved by controlled exposure to light. We have designed, synthesized and tested a series of novel PS porphyrin derivatives for their effectiveness at killing triple-negative breast cancer cells <i>in vitro</i>. Each contains a tetraphenyl-porphyrin core; a series of related side groups have been conjugated to the benzene rings to vary the properties of the derivatives. As a control we have used Foscan, which is a chlorin-based PS approved in the EU and in clinical trials in the US. Each derivative has been tested for phototoxicity in the light and in the dark. All show concentration-dependent killing in the light and several are effective in the low micromolar range. All show minimal toxicity in the dark at low concentrations. We have also tested how well several of the compounds are taken up by cells <i>in vitro</i>. We have not detected a consistent relationship between uptake and either phototoxicity or dark toxicity. While these derivatives are not as effective as Foscan at submicromolar concentrations and require higher doses of light for the same level of toxicity, this may provide a way to reduce unwanted toxicity to skin cells from exposure to ambient light, which is one of the primary side-effects of PDT.

Novel porphyrin derivatives for photodynamic therapy

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.