Light-induced skin extracellular matrix remodelling through ROS generation: highlighting the potential of sublethal-photodynamic therapy – LUMOS

In LUMOS project we propose an innovative strategy consisting in deviating the classical antitumor use of photodynamic therapy (PDT), a ROS-generating technology, to locally modulate ECM in a calibrated manner. A pluridisciplinary and multiscale approach ranging from collagens’ structural organization to functional properties of tissue will be conducted on sophisticated, normal or aged-, human skin substitutes in order to determine how photosensitizers associated or not with nanomedicine acts on ECM remodelling.

The experiments are currently being carried out by the 3 partners. The results will be presented as soon as they have been validated by scientific publications.

At the end of the project, we will be able to propose a table of the relations between the nature of the photosensitizer / its photochemical properties / the induced cellular pathways at skin tissue level in a context of ECM remodelling. The fundamental knowledge generated by LUMOS project will be essential to propose a controllable and tunable photochemical approach to efficiently promote local ECM remodelling and strengthening via ROS modulation. Finally, since PDT is nowadays well established in clinics, our original therapeutic approach presents a high and easy translational potential.

Impairment in extracellular matrix (ECM) regulation is involved in cancers and fibrosis and therefore represents a promising therapeutic target. Our aim is to focus on the positive effects that reactive oxygen species (ROS) exert on ECM remodeling. Indeed, in LUMOS project we propose an innovative strategy consisting in deviating the classical antitumor use of photodynamic therapy (PDT), a ROS-generating technology, to locally modulate ECM in a calibrated manner. A pluridisciplinary and multiscale approach ranging from collagens’ structural organization to functional properties of tissue will be conducted on sophisticated, normal or aged-, human skin substitutes in order to determine how photosensitizers associated or not with nanomedicine acts on ECM remodelling. Our project offers a rare opportunity to develop a photochemical toolbox to modulate “on-demand” ECM environment for broad-spectrum therapeutic needs especially in dermatology and cosmetics. The strength of our project is undeniably the critical and complete description of the ECM components (direct effects) and cellular (indirect effects) responses induced by the calibrated-PDT, depending on the nature and the formulation (encapsulated or not) of photosensitizer, in a relevant tissue model close to in vivo reality. Indeed, at the end of the project, we will be able to propose a table of the relations between the nature of the photosensitizer / its photochemical properties / the induced cellular pathways at skin tissue level in a context of ECM remodelling. The fundamental knowledge generated by LUMOS project will be essential to propose a controllable and tunable photochemical approach to efficiently promote local ECM remodelling and strengthening via ROS modulation. Finally, since PDT is nowadays well established in clinics, our original therapeutic approach presents a high and easy translational potential.