Hybrid Nanoparticles as Theranostics Platforms for Glioblastoma Treatment: Phototherapeutic and X-ray Phase Contrast Tomography Investigations

Abstract

Glioblastoma multiforme (GBM) is one of the deadliest and most aggressive cancers, remarkably resilient to current therapeutic treatments. Here, we report preliminary in vivo studies of GBM treatments based on photo-nanotherapeutics to activate synergistic killing mechanisms. Core-shell nanoparticles have been weaponized by combining photophysical properties of a new generation PDT agent (Ir(III) complex) with the thermoplasmonic effects of resonant gold nanospheres. In order to investigate the damages induced in GBM treated with these photoactivable nanosystems, we employed X-ray phase-contrast tomography (XPCT). This high-resolution three-dimensional imaging technique highlighted a vast devascularization process by micro-vessels disruption, which is indicative of tumor elimination without relapse.

Bispecific aptamer-decorated and light-triggered nanoparticles targeting tumor and stromal cells in breast cancer derived organoids: implications for precision phototherapies

“…Multifunctional gold-core/silica-shell nanoparticles embedding the photosensitizing and luminescent molecule Ir en [ 41 ] were synthesized following a previously reported protocol [ 17 , 18 ] with slight modifications. Briefly, quaternary water/oil (W/O) microemulsion was prepared by mixing 3.6 mL of Triton X-100, 3.6 mL of n-hexanol, 15 mL of cyclohexane and a water solution consisting of 0.9 mL HAuCl 4 ·3H 2 O (12.75 mM), 0.9 mL Mesna (36.5 mM) and 0.3 mL NaBH 4 (423 mM).…”

“…Both treatment approaches, as well as to the possibility of being used in combination to develop synergistic effects [15], ensure a high spatio-temporal control of the cytotoxic activity in the limited area exposed to irradiation, thus limiting systemic side effects. In this frame, we have previously reported the synthesis and characterization of a multifunctional nanoplatform for combined PDT and PTT treatments, based on a goldcore and silica-shell structure, embedding in the polysiloxane matrix an iridium(III) compound ([Ir(ppy) 2 (en)] OOCCH 3 , where ppy = 2-phenylpyridine and en = ethylenediamine, Ir en ), employed as photosensitizer and luminescent probe [17,18].…”