title: Self-assembled polymeric vectors mixtures: characterization of the polymorphism and existence of synergistic effects in photodynamic therapy.
abstract: The objective of this work was to assess the relation between the purity of polymeric self-assemblies vectors solution and their photodynamic therapeutic efficiency. For this, several amphiphilic block copolymers of poly(ethyleneoxide-b-ε-caprolactone) have been used to form self-assemblies with different morphologies (micelles, worm-like micelles or vesicles). In a first step, controlled mixtures of preformed micelles and vesicles have been characterized both by dynamic light scattering and asymmetrical flow field flow fractionation (AsFlFFF). For this, a custom-made program, STORMS, was developed to analyze DLS data in a thorough manner by providing a large set of fitting parameters. This showed that DLS only sensed the larger vesicles when the micelles/vesicles ratio was 80/20 w/w. On the other hand, AsFlFFF allowed clear detection of the presence of micelles when this same ratio was as low as 10/90. Subsequently, the photodynamic therapy efficiency of various controlled mixtures was assessed using multicellular spheroids when a photosensitizer, pheophorbide a, was encapsulated in the polymer self-assemblies. Some mixtures were shown to be as efficient as monomorphous systems. In some cases, mixtures were found to exhibit a higher PDT efficiency compared to the individual nano-objects, revealing a synergistic effect for the efficient delivery of the photosensitizer. Polymorphous vectors can therefore be superior in therapeutic applications.
authors.affiliation: Université de Toulouse, Institut National Polytechnique de Toulouse-Ecole d'Ingénieurs de Purpan, Département Sciences Agronomiques et Agroalimentaires, 75 voie du TOEC, BP 57611, F-31076 Toulouse Cedex 03, France. Laboratoire des IMRCP, Université de Toulouse, CNRS UMR 5623, Université Paul Sabatier, 118 route de Narbonne, F-31062, Toulouse Cedex 9, France.
authors.forename: Ugo
authors.initials: U
authors.lastname: Till
authors.forename: Laure
authors.initials: L
authors.lastname: Gibot
authors.forename: Christophe
authors.initials: C
authors.lastname: Mingotaud
authors.forename: Patricia
authors.initials: P
authors.lastname: Vicendo
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Rols
authors.forename: Mireille
authors.initials: M
authors.lastname: Gaucher
authors.forename: Frédéric
authors.initials: F
authors.lastname: Violleau
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Mingotaud
mesh_terms: D008823:Micelles; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D011108:Polymers / Q000737:chemistry*
chemical_list: D008823:Micelles; D017319:Photosensitizing Agents; D011108:Polymers