New Generation of Porphyrinoids for Mitochondria-targeted Photodynamic Therapy (PROMPT)
PROMPT is a Marie Skłodowska-Curie Individual Fellowship (IF) Action funded by the European Union Framework Programme for Research and Innovation Horizon 2020 (Grant agreement ID: 798952). The project is ongoing since January 2019 and will complete by December 2020.
The project information and funding details can be viewed at CORDIS page: https://cordis.europa.eu/project/id/798952/en
PROMPT is a multidisciplinary project that involves experts from various backgrounds ranging from synthetic chemistry, photochemistry and biological sciences.
|Consiglio Nazionale delle Ricerche||Istituto per la Sintesi Organica e la Fotoreattività||Bologna, Italy||Dr. Sabarinathan Rangasamy (MSCA Fellow)|
|Consiglio Nazionale delle Ricerche||Istituto per la Sintesi Organica e la Fotoreattività||Bologna, Italy||Dr. Barbara Ventura (Supervisor)|
|Université de Strasbourg||Institut de Chimie, Laboratoire LSAMM||Strasbourg, France||Prof. Valérie Heitz (Collobrator)|
|Université de Strasbourg||CAMB, Faculté de Pharmacie||Strasbourg, France||
Prof. Frederic Bolze (Collobrator)
|Consiglio Nazionale delle Ricerche||Istituto per i Sistemi Biologici||Rome, Italy||Dr. Cecilia Bombelli (Collobrator)|
Cancer is among the principal causes of death worldwide. According to the World Health Organization (WHO), there were 18.1 million new cases and 9.6 million deaths in the year 2018. Among them, Lung, colon, prostate, and breast cancers are the most common cause of death (see figure below). The occurrence of cancer death can be considerably decreased by a correct and early diagnosis and effective treatment. Every cancer type is handled with a specific treatment regimen which might encompass one or more modalities such as surgery, radiotherapy, chemotherapy, and more recently, photodynamic therapy (PDT).
PDT is a light-based therapeutic modality in which a photosensitizer (PS), upon light excitation in the UV-Vis region and efficient population of a triplet excited state, produces cytotoxic molecular species via electron transfer to biological substrates and/or molecular oxygen (type I photosensitization), or energy transfer to molecular oxygen (type II photosensitization) producing singlet oxygen, a known reactive species. Because of these phenomena, PDT is considered to be a non-invasive treatment strategy for different types of cancer. Further, it can be used as a combination treatment along with other cancer therapies including surgery, chemotherapy, radiation therapy and gene therapy without affecting their therapeutic modalities.
Targeting subcellular organelles is the prime concept. The preparation of an ideal photosensitizer for PDT presents significant challenges. Traditionally, porphyrin-type macrocycles have been explored as PDT sensitizers. Hematoporphyrin derivative (HpD) and Photofrin are gold standards in PDT and considered as first-generation PSs. Second generation PSs were developed to overcome problems encountered in the first generation molecules, such as the mixture of compounds, prolonged skin photosensitization, and lack of deep tissue penetration. These compounds are chemically pure and absorb light at longer wavelengths. Further to their improvement, PSs were linked to carriers such as antibodies and liposomes for selective localization within tumor tissues and were referred to as third-generation PSs. In this scenario, PROMPT aims at the development of novel porphyrin-type and corrole-type photosensitizers to target subcellular organelles, specifically mitochondria, in order to mediate apoptotic cell death during PDT. This project is interdisciplinary, merging competences from synthetic chemistry to cell biology, photophysics and microscopy.
The specific training and research motives are:
- Design and synthesis of meso-substituted porphyrins containing aromatic heterocyclic groups
- Photophysical characterization of porphyrin macrocycles by means of steady-state and time-resolved optical techniques
- Biological assays on the new compounds to evaluate PDT activity under dark and light conditions
- One-photon and Two-photon PDT in live cancerous cell
- Liposomal formulation to enhance drug solubility and targeting
- Participation and presentation of a poster on "Mitochondria-targeted Porphyrinoids: A New Class of Photosensitizer for One and Two-photon Targeted Photodynamic Therapy" at the Annual Congress of the Italian Society of Photobiology – SIFB 2019.
- Participation and presention of a poster on "New generation of Porphyrinoids for Mitochondria-targeted Photodynamic Therapy" at UK-Italy joint meeting on photochemistry 2019.
- The significance of the PROMPT project was disseminated among the public at the European Researchers' Night 2019 in Bologna.