PROMPT · New generation of porphyrinoids for mitochondria-targeted photodynamic therapy
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-01-01 → 2020-12-31
- EU contribution
- €168,277
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
New generation of porphyrinoids for mitochondria-targeted photodynamic therapy
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.
Data: CORDIS, © European Union
Project objective
PROMPT will develop a new generation of photosensitizers targeting mitochondria in cancer cells, to be used in photodynamic therapy (PDT). The innovative approach of PROMPT is based on the design and synthesis of porphyrinoids functionalized with aromatic heterocyclic groups containing C-S bonds. These molecules are expected to localize specifically in mitochondria of cancer cells and to efficiently generate singlet oxygen, leading to apoptosis induction and cell death. Loading of the photosensitizers into liposomes ad hoc functionalized to target mitochondria is also envisaged in case of need. The innovative photodynamic treatment will thus show high selectivity, lower dose of treatment and reduced side effects with respect to the presently used phototherapy approaches. Moreover, the new molecules are expected to show significant two-photon absorption properties, due to the extended conjugation of the porphyrinoid core introduced by the aromatic side groups. They will thus represent a groundbreaking class of mitochondria-targeted photosensitizers for both one- and two-photon PDT. The multidisciplinarity of PROMPT, together with the proposed work plan in a forefront area of bio-medical research, will widen the scientific skills and technological know-how of the Experienced Researcher, significantly improving his career opportunities both in the academic and private sectors.
Original text from CORDIS.
Participants
- CONSIGLIO NAZIONALE DELLE RICERCHE · RomaCoordinatorItaly
Links
Data: CORDIS, © European Union