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

Laure Gibot (1, 2) , Maxime Demazeau (1, 2) , Véronique Pimienta (1, 2) , Anne-Françoise Mingotaud (1, 2) , Patricia Vicendo (1, 2) , Fabrice Collin (1, 3) , Nathalie Martins-Froment (4) , Stéphane Dejean (5) , Benjamin Nottelet (5) , Clément Roux (1, 2) , Barbara Lonetti (1, 2)

1 IMRCP - Interactions moléculaires et réactivité chimique et photochimique
2 IMRCP - IDeAS - IMRCP - Interfaces Dynamiques et Assemblages Stimulables
3 IMRCP - BIBAC - IMRCP - Chimie analytique et interactions biomolécules - matière molle biomimétique
4 ICT - Institut de Chimie de Toulouse
5 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

The use of nanocarriers for hydrophobic photosensitizers, in the context of photodynamic therapy (PDT) to improve pharmacokinetics and bio-distribution, is well-established. However, the mechanisms at play in the internalization of nanocarriers are not well-elucidated, despite its importance in nanocarrier design. In this study, we focus on the mechanisms involved in copolymer poly(ethylene oxide)-block-poly(-caprolactone) PEO-PCL and poly(ethylene oxide)-block-poly styrene PEO-PS micelles - membrane interactions through complementary physico-chemical studies on biomimetic membranes, and biological experiments on two-dimensional (2D) and three-dimensional (3D) cell cultures. Förster Resonance Energy Transfer measurements on fluorescently-labelled lipid vesicles, and flow cytometry on two cancerous cell lines enabled the evaluation in 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 in delivering 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 demonstrated that there are subtle differences in PEO-PCL and PEO-PS micelles for the delivery of Pheo.

Mots clés: PEO-PCL; PEO-PS; Photodynamic therapy; Polymer; Self-assembly; model membranes

Domaines: Polymères; Chimie; Sciences du Vivant [q-bio]; Biologie cellulaire

Laure Gibot, Maxime Demazeau, Véronique Pimienta, Anne-Françoise Mingotaud, Patricia Vicendo, et al.. Role of Polymer Micelles in the Delivery of Photodynamic Therapy Agent to Liposomes and Cells. Cancers, 2020, 12 (2), pp.384. ⟨10.3390/cancers12020384⟩. ⟨hal-02565671⟩