New Targeted Gold Nanorods for the Treatment of Glioblastoma by Photodynamic Therapy.
Fiche publication
Date publication
décembre 2019
Journal
Journal of clinical medicine
Auteurs
Membres identifiés du Cancéropôle Est :
Dr FROCHOT Céline, Dr VANDERESSE Régis
Tous les auteurs :
Youssef Z, Yesmurzayeva N, Larue L, Jouan-Hureaux V, Colombeau L, Arnoux P, Acherar S, Vanderesse R, Frochot C
Lien Pubmed
Résumé
This study describes the employment of gold nanorods (AuNRs), known for their good reputation in hyperthermia-based cancer therapy, in a hybrid combination of photosensitizers (PS) and peptides (PP). We report here, the design and the synthesis of this nanosystem and its application as a vehicle for the selective drug delivery and the efficient photodynamic therapy (PDT). AuNRs were functionalized by polyethylene glycol, phototoxic pyropheophorbide-a (Pyro) PS, and a "KDKPPR" peptide moiety to target neuropilin-1 receptor (NRP-1). The physicochemical characteristics of AuNRs, the synthesized peptide and the intermediate PP-PS conjugates were investigated. The photophysical properties of the hybrid AuNRs revealed that upon conjugation, the AuNRs acquired the characteristic properties of Pyro concerning the extension of the absorption profile and the capability to fluoresce (Φ = 0.3) and emit singlet oxygen (Φ = 0.4) when excited at 412 nm. Even after being conjugated onto the surface of the AuNRs, the molecular affinity of "KDKPPR" for NRP-1 was preserved. Under irradiation at 652 nm, in vitro assays were conducted on glioblastoma U87 cells incubated with different PS concentrations of free Pyro, intermediate PP-PS conjugate and hybrid AuNRs. The AuNRs showed no cytotoxicity in the absence of light even at high PS concentrations. However, they efficiently decreased the cell viability by 67% under light exposure. This nanosystem possesses good efficiency in PDT and an expected potential effect in a combined photodynamic/photothermal therapy guided by NIR fluorescence imaging of the tumors due to the presence of both the hyperthermic agent, AuNRs, and the fluorescent active phototoxic PS.
Mots clés
NRP-1, PDT, glioblastoma, gold nanorods, peptide, photosensitizer, targeting
Référence
J Clin Med. 2019 Dec 13;8(12):