Role of Polymer Micelles in the Delivery of Photodynamic Therapy Agent to Liposomes and Cells
by
Laure Gibot 1,†
, Maxime Demazeau 1,†, Véronique Pimienta 1, Anne-Françoise Mingotaud 1, Patricia Vicendo 1, Fabrice Collin 1, Nathalie Martins-Froment 2, Stéphane Dejean 3, Benjamin Nottelet 3, Clément Roux 1,* and Barbara Lonetti 1,*
Laure Gibot 1,†, Maxime Demazeau 1,†, Véronique Pimienta 1, Anne-Françoise Mingotaud 1, Patricia Vicendo 1, Fabrice Collin 1, Nathalie Martins-Froment 2, Stéphane Dejean 3, Benjamin Nottelet 3, Clément Roux 1,* and Barbara Lonetti 1,*
1
Laboratoire des IMRCP, Université de Toulouse, CNRS UMR 5623, Université Toulouse III—Paul Sabatier, F-31062 Toulouse, France
2
Service Commun de Spectrométrie de Masse (FR2599), Université de Toulouse III (Paul Sabatier), 118, route de Narbonne, F-31062 Toulouse Cedex 9, France
3
IBMM, Université de Montpellier, CNRS, ENSCM, 34 090 Montpellier, France
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(2), 384; https://doi.org/10.3390/cancers12020384
Received: 8 January 2020 / Revised: 29 January 2020 / Accepted: 4 February 2020 / Published: 7 February 2020
(This article belongs to the Special Issue Photodynamic Therapy (PDT) in Oncology)
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(ε-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.
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Keywords:
Photodynamic therapy; Self-assembly; Polymer; PEO-PCL; PEO-PS; model membranes
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MDPI and ACS Style
Gibot, L.; Demazeau, M.; Pimienta, V.; Mingotaud, A.-F.; Vicendo, P.; Collin, F.; Martins-Froment, N.; Dejean, S.; Nottelet, B.; Roux, C.; Lonetti, B. Role of Polymer Micelles in the Delivery of Photodynamic Therapy Agent to Liposomes and Cells. Cancers 2020, 12, 384.
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