Self assembled copolymers nanoparticles. From the first correlations structure-biological function to applications to the photodynamic therapy – COPOPDT

Delivery of photosensitizers by copolymer micelles: From the mechanism to the application in photodynamic therapy.
The design of drug delivery strategies represents a major challenge to efficiently fight against diseases with minimal side effects. For water insoluble drugs, formulation is a prerequisite. Due to their versatile structure and their biocompatibility, block copolymer micelles (NPs) are very attractive nano-carriers that start to be explored by pharmaceutical companies. However, only limited information is available on their interactions with cells, tissues and the release of the loaded drug. This work will allow establishing correlations between the architecture of these NPs and their biological activity. Among other targeted therapies, photodynamic therapy (PDT) has received much attention over the recent years for selective
Référence du formulaire : ANR-FORM-090601-01-01 5/21
treatment of tumors. This innovative therapy relies on a local light excitation of a photosensitizer (PS). As many PS are poorly water soluble, formulation is most often required. The final goal of this project is to understand the drug delivery mechanisms of copolymer micelles and to use them for the passive targeting of PS in PDT.This program in fundamental research is likely to be extended to industrial problems. One of its originality is to be at the convergence point between nano-objects, biosciences and health.
"Asymmetric Flow Field Flow Fractionation," and fluorescence energy transfer: determination of the drug delivery mechanism of copolymer micelles.
Different block copolymers micelles with reproducible size were prepared in biocompatible conditions. NP were characterized by conventional techniques and "Asymmetric Flow Field Flow Fractionation," (AF4) which allows evaluating the PS loading rate The influence of the chemical structure of the block copolymers on the stability upon dilution of the polymeric micelles and aging was assessed by FRET experiment and dialysis under various experimental conditions (alone or in the presence of blood proteins). At the biological level, the studies were performed on 2D and 3D cell culture models from breast and colon cancer cells. Uptake and cellular localization, toxicity and phototoxicity of the carriers with or without their load were evaluated by confocal microscopy and flow cytometry. The drug delivery mechanisms of the copolymer micelles were determined on membrane models by FRET experiments.