PDTeam’s project : Targeting to improve PDT selectivity

Since 15 years, our main goal consists in improving the selectivity of PDT treatment. Different strategies are developed in Nancy by the PDTeam. The ability to directly target a therapeutic agent to a tumoral site minimizes systemic drug exposure, thus providing the potential for increasing the therapeutic index. Selective accumulation of the photosensitizers in cancer cells or neo-vasculature is required to avoid collateral damages. We develop (i) photosensitizers coupled to moieties such as folic acid (in collaboration with INSERM ONCOTHAI, U1189, Lille) to directly target receptors over-expressed on ovarian peritoneal metastasis [[1], [2], [3]], (ii) photosensitizers coupled to peptides (in collaboration with UMR 7369, CNRS-URCA, Reims) to directly target LRP-1 overexpressed on glioblastome cancerous cells, (iii) multifunctional nanoparticles coupled to peptide (in collaboration with ILM, UMR 5306 CNRS-Universite Claude Bernard, Lyon) to target NRP-1 over-expressed on neo-vessels [[4], [5]]. We also design scintillating nanoparticles that allow the combination of radiotherapy and PDT. Novel hybrid system of scintillating nanoparticles and PDT photosensitizers enable excitation of the constructed nano-devices using by X-rays, which can penetrate deeply into tissues [[6], [7]]. This new modality could allow treatment of deep tumors using lower radiation dose than conventional radiotherapy. The last strategy is the elaboration of photomolecular beacons, to produce reactive oxygen species specifically at the tumoral site. This approach consists in using the activity of enzymatic cleavage of biomarkers over-expressed in tumoral areas such as matrix metalloproteinases (MMPs) [8].