Design of a Targeting and Oxygen-Independent Platform to Improve Photodynamic Therapy: A Proof of Concept.
Fiche publication
Date publication
février 2021
Journal
ACS applied bio materials
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FROCHOT Céline, Pr BOURA Cédric
Tous les auteurs :
Larue L, Moussounda Moussounda Koumba T, Le Breton N, Vileno B, Arnoux P, Jouan-Hureaux V, Boura C, Audran G, Bikanga R, Marque SRA, Acherar S, Frochot C
Lien Pubmed
Résumé
Photodynamic therapy (PDT) is a promising technique to treat different kinds of disease especially cancer. PDT requires three elements: molecular oxygen, a photoactivatable molecule called the photosensitizer (PS), and appropriate light. Under illumination, the PSs generate, in the presence of oxygen, the formation of reactive oxygen species including singlet oxygen, toxic, which then destroys the surrounding tissues. Even if PDT is used with success to treat actinic keratosis or prostate cancer for example, PDT suffers from two major drawbacks: the lack of selectivity of most of the PSs currently used clinically as well as the need for oxygen to be effective. To remedy the lack of selectivity, targeting the tumor neovessels is a promising approach to destroy the vascularization and cause asphyxia of the tumor. KDKPPR peptide affinity for the neuropilin-1 (NRP-1) receptor overexpressed on endothelial cells has already been proven. To compensate for the lack of oxygen, we focused on photoactivatable alkoxyamines (Alks), molecules capable of generating toxic radicals by light activation. In this article, we describe the synthesis of a multifunctional platform combining three units: a PS for an oxygen-dependent PDT, a peptide to target tumor neovessels, and an Alk for an oxygen-independent activity. The synthesis of the compound was successfully carried out, and the study of its photophysical properties showed that the PS retained its capacity to form singlet oxygen and the affinity tests confirmed the affinity of the compound for NRP-1. Thanks to the electron paramagnetic resonance spectroscopy, a technique of choice for radical investigation, the radicals generated by the illumination of the Alk could be detected. The proof of concept was thus successfully established.
Mots clés
alkoxyamine, hemolysis, hypoxia, neuropilin-1, peptide, photodynamic therapy, spin trapping, targeting
Référence
ACS Appl Bio Mater. 2021 Feb 15;4(2):1330-1339