Conception et optimisation de nanoparticules dendrimériques photoactivables dans le cadre d’un traitement photodynamique

Abstract : Photodynamic therapy (PDT) is a modality of cancer treatment, involving a combined action of molecular oxygen, light and photosensitizers (PS). However, the PSs suffer from a low solubility in aqueous media and limited tumor accumulation, diminishing the treatment success. Presently, particular attention is paied to the development of dendrimer-based nanoparticles (NP) that are able to overcome the shortcomings of the PSs. The present study investigates the poly(amidoamine) dendrimer (PAMAM), a tridimensional polymeric macromolecule, covalently functionalized with the PS Chlorin e6 (Ce6). The singlet oxygen generation efficiency and fluorescence emission were moderately affected by the covalent binding of the Ce6 to the dendrimer. This construction allows the vectorization of 32 Ce6 molecules per dendrimer. In vitro, PAMAM dendrimers improve the PDT efficiency of Ce6 by promoting their cellular internalization via an active endocytosis mechanism. However, the PDT efficiency of NPs is limited by the high local concentration of Ce6 at the periphery of dendrimers decreasing production of singlet oxygen. Ce6 release could restore Ce6 photophysical properties and as such improve the PDT efficiency of NP. Thus, the next step of this work was to design a cleavable NP able to release the Ce6 under esterase activity. In solution the NP characterization demonstrated that the photophysical properties of Ce6 were recovered after their release from the NP. This cleavable construction displays promising perspectives for future PDT applications
Document type :
Theses
Complete list of metadatas

Cited literature [221 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/tel-01754629
Contributor : Thèses Ul <>
Submitted on : Friday, March 30, 2018 - 9:55:31 AM
Last modification on : Sunday, April 1, 2018 - 1:17:01 AM

File

DDOC_T_2015_0322_BASTIEN.pdf
Files produced by the author(s)

Identifiers

  • HAL Id : tel-01754629, version 1

Citation

Estelle Bastien. Conception et optimisation de nanoparticules dendrimériques photoactivables dans le cadre d’un traitement photodynamique. Médecine humaine et pathologie. Université de Lorraine, 2015. Français. ⟨NNT : 2015LORR0322⟩. ⟨tel-01754629⟩

Share

Metrics

Record views

62

Files downloads

86