Photodynamic therapy (PDT) is a developing and highly promising non-invasive treatment modality for certain cancer types and it has been widely studied during the last decades. In PDT, therapeutic action is satisfied by the generation of singlet oxygen (1O2) upon irradiation of well-designed PDT agents (photosensitizers or drugs) by light. Singlet oxygen is the excited form of molecular oxygen (3O2) and it is cytotoxic due to its high reactivity towards vital biomolecules. In addition to this oxidative damage triggered direct killing mode (apoptosis or necrosis) arises from 1O2 reactivity, PDT also restricts the follow of nutrients and oxygen to cancer cells by disturbing the vasculatures around tumour regions and at the same time activates the immune system against cancer cells. The advantages and importance of PDT are more pronounced when it is compared with widely used conventional chemotherapy and radiotherapy, since these therapies have numerous side effects and they give serious damage to the immune system. Although PDT is highly promising, its broader applicability in clinical treatments is restricted due to some problems. The most important one is the limited penetration of the irradiation light through tissues, which leaves the deeper tumours out from the scope of PDT. Studies have shown that red or near-IR absorbing PDT agents should be employed to get the best penetration depth and to avoid the absorption of incoming light by biomolecules. Although, a very wide range of well-known fluorescent probe cores have been converted to PDT agents, red and near-IR absorbing PDT agents are rare. Another important challenge that new PDT drugs should address is the activation of singlet oxygen only in cancer cells without giving harm to healthy cells.1 In this direction, cancer cell selective and activatable PDT agents are highly needed. In this study, a very well-known red absorbing resorufin fluorophore core have been converted to a cytotoxic and enzyme-activated PDT drug for the first time. Two resorufin-based PDT drugs are introduced; one of them is activated selectively by b-galactosidase in ovarian cancer cells and the second one is cytotoxic only in the presence of monoamine oxidase (MAO) in cervical cancer cells. Therapeutic effect of PDT drugs is analysed with in vitro cell culture studies.

New class of red absorbing activatable PDT drugs

2019 Spring National Meeting

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