COMBPDCHEMOTHERAPY · Rational design of combined PDT photosensitizers and chemotherapeutic agent as new approach in cancer therapy: a computational approach
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-07-01 → 2017-06-30
- EU contribution
- €173,076
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Rational design of combined PDT photosensitizers and chemotherapeutic agent as new approach in cancer therapy: a computational approach
To increase the effectiveness of anticancer therapy, the combination of multimodal treatment methods into a single synergistic system is a very promising approach. One of the newest and most challenging strategies, still in its infancy, is to functionalize a photosensitizer suitable for application in Photodynamic Therapy (PDT), with a cisplatin-like compound, thus combining PDT effect and cytostatic activity. These conjugates are able to promote a better distribution Pt-mediated of the PS within the tumour and to address the several drawbacks associated with the classic Pt-chemotherapy. The search for the ideal photosensitizer is very much under way and the information that can be gained from computational studies is very useful, as it has the potential to increase the understanding of the entire photochemical pathways involved. The overall aim of the COMBPDCHEMOTHERAPY was to 1) establish the most appropriate computational protocol investigating the crucial photophysical properties of selected combined PDT and chemotherapeutic agents, gaining information and useful guidelines; 2) Investigate members of novel and very interesting classes of bioactive molecules of interest as anti-cancer agents able to afford a dual action in killing cancer cells. Form one side we were interested in promising assemblies consisting of a light-absorber chromophore (PS) and a cisplatin-like unit. On the other hand, we were also interested in dyads characterized by a low-lying 3IL state able to afford a dual Type I/Type II action depending on the oxygen tension in the tissues. The rationalization of the photophysical properties of existing classes of photosensitizers allowed us to gain rational guidelines to propose the design of novel photosensitizers with desired molecular properties.
Data: CORDIS, © European Union
Project objective
The present proposal aims to enhance the competences, the scientific and innovative potential of the experienced researcher in the field of the emerging non-invasive treatment of a variety of cancer tumour types called photodynamic therapy (PDT). This approach induces tumour cells necrosis and/or apoptosis by a combination of a photosensitising drug (PS) capable of absorbing within the body’s therapeutic window (620–850 nm), a light source (e.g.,a laser) of an appropriate wavelength and molecular oxygen. To further advance the novel PDT treatment, the design, synthesis and characterisation of new photosensitizers with improved efficiency and side effect profiles is needed, together with a more thorough and integrated understanding of the multitude of targets/actions so far ascribed to PDT. In this field, the information that can be gained from modern theoretical methods is very useful, since several crucial chemical and physical properties of candidate photosensitizers can be accurately predicted from first principles by various computational techniques, contributing to increase the understanding of the entire photochemical pathways involved. The “a priori” knowledge of a series of properties can be considered a basic requirement before proceeding to the synthesis, chemical-physical characterisation and in vitro and in vivo tests, thus orienting experimental planning and avoiding expensive and time-consuming experiments. The project attempts to investigate members of a novel and very interesting class of bioactive molecules of interest as anti-cancer agents, consisting of a light-absorber chromophore (PS) and a cisplatin-like unit. The two-component conjugates combine the cytostatic activity of the platinum moiety in the dark, and upon irradiation, the photodynamic action of the sensitizer. Such systems could address the restrictions of Pt-based complexes and provide a target for PDT agents, while maintaining efficient DNA binding and photocleaving properties.
Original text from CORDIS.
Participants
- ECOLE NATIONALE SUPERIEURE DE CHIMIE DE PARIS · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union