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

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 degrees 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 degrees 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. (c) 2024 American Pharmacists Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.