Cancer is the leading cause of death worldwide. The Global Cancer Observatory (GLOBOCAN) has estimated that the global burden of cancer has risen to 19.3 million new cases and 10.0 million deaths in 2020, also predicting that the new cancer cases will increase to 32.2 million in 2040. Due to these alarming facts, it is necessary to improve cancer diagnostic methods and treatments. Every cancer type is handled with a specific treatment regimen that might encompass one or more modalities, such as surgery, radiotherapy, chemotherapy, and the more recently explored photodynamic therapy (PDT).
PDT is a non-invasive treatment strategy for different types of cancer, based on the use of light. It requires a photosensitizer (PS) which, upon light irradiation in the UV-Vis region, undergoes intersystem crossing to its triplet excited state. Eventually, the latter, reacting with molecular oxygen, generates cytotoxic species that induce cell death. The development of PSs has been recently focussed on targeting subcellular organelles, as a powerful tool to reduce side effects in healthy tissues and organs. Moreover, the possibility of two-photon (TP) excitation of the photosensitizer leads to several advantages, inherent to the TP absorption phenomenon: excitation in the biological window (700-1000 nm) where tissues have negligible absorption and reduced scattering, combined with a spatially confined and less invasive treatment.
To address these issues, the overall objective of PROMPT is the development of novel porphyrin one- and two-photon photosensitizers to selectively target mitochondria in cancer cells.
The target photosensitizer should be chemically pure and have low dark toxicity, high quantum yield of reactive oxygen species (ROS), high cellular uptake, and rapid clearance from the body to avoid phototoxic side effects. The PROMPT project is expected to deliver improvements in:
1. Absorption and emission properties of the PSs (high molar absorption coefficients and enhanced fluorescence quantum yields);
2. High singlet oxygen quantum yields;
3. Selective targeting of mitochondria in cancerous cells for apoptotic cell death;
4. Improved efficacy of one and two-photon photodynamic therapy.
