Targeted thermosensitive liposomes loaded with gold nanoparticles and temozolomide hexadecanoate for the synergistic photothermal-chemotherapy treatment of glioblastoma

Abstract

Glioblastoma (GBM) is a highly aggressive malignant brain tumour which presents a significant challenge due to the limited effectiveness of current surgical and chemotherapeutic approaches. In this study, we have developed TMZ16e and gold nanoparticles coencapsulated thermosensitive liposomes modified with anti-EphA3 (anti-EphA3-TMZ16e-GNPs-TSL) delivered via the intranasal route to achieve photothermal chemotherapy (PCT) for improving the therapeutic effects of GBM. The prepared anti-EphA3-TMZ16e-GNPs-TSL were spherical with a particle size of 173.7±1.2 nm with toxicity tests confirming their excellent safety for the nasal mucosa. Furthermore, an elevated temperature (42.2°C) was observed under 780 nm infrared irradiation, which resulted in the targeted release of TMZ16e. In vitro, cellular assays demonstrated that the cytotoxicity in the anti-EphA3-TMZ16e-GNPs-TSL group were significantly higher (55%) than other groups upon laser irradiation (p < 0.01). In vivo, thermographic analysis revealed a significant increase in brain temperature (42.4°C) in the anti-EphA3-TMZ16e-GNPs-TSL group. The combination therapy resulted in a significant increase in tumor cell apoptosis and a median survival time of 47 days, which was 1.38 and 1.68 times longer than that observed in rats treated with chemotherapy or photothermal therapy, respectively. H&E and TUNEL staining results that PCT induce apoptosis in GBM cells. This targeted PCT system represents a promising treatment strategy for GBM, offering a more precise and potent therapeutic intervention that could potentially improve patient prognosis and quality of life.

Keywords: Glioblastoma;Photothermal-chemotherapy;Thermosensitive liposomes;Gold nanoparticles;Temozolomide hexadecanoate.