Role of Polymer Micelles in the Delivery of Photodynamic Therapy Agent to Liposomes and Cells

ABSTRACT

The use of nanocarriers for hydrophobic photosensitizers in the context of photodynamic therapy (PDT) to improve pharmacokinetics and biodistribution is well established. However, the mechanisms at play in the internalization of nanocarriers are not well elucidated despite being crucial to inspiring nanocarrier design. Here we focus on the mechanisms involved in copolymer PEO-PCL and PEO-PS micelles – membrane interactions through complementary physico-chemical studies on biomimetic membranes and biological experiments on 2D and 3D cell cultures. Förster Resonance Energy Transfer measurements on fluorescently labelled lipid vesicles and flow cytometry on two cancerous cell lines allowed evaluation of the uptake of a photosensitizer, Pheophorbide a (Pheo), and copolymer chains towards model membranes and cells respectively. The effects of calibrated light illumination for PDT treatment on lipid vesicle membranes, i.e. leakage and formation of oxidized lipids, and cell viability, were assessed. No significant differences were observed between the ability of PEO-PCL and PEO-PS micelles to deliver Pheo to model membranes, but Pheo was found in higher concentrations in cells in the case of PEO-PCL. These higher Pheo concentrations did not correspond to better performances in PDT treatment. We thus highlighted subtle differences in PEO-PCL and PEO-PS micelles for the delivery of Pheo.