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

in Journal of pharmaceutical sciences by Xinliu Duan, Aiping Wang, Li Jiang, Xuan Zhou, Jiewen Zhao, Xu Deng, Liuxiang Chu, Yueli Liu, Yanyan Jiang, Wenjing Song, Kaoxiang Sun

TLDR

  • A new treatment for Glioblastoma (GBM) using photothermal chemotherapy (PCT) with thermosensitive liposomes coencapsulated with TMZ16e and gold nanoparticles modified with anti-EphA3 showed promise in improving patient prognosis and quality of life.

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.

Overview

  • The study aims to develop a new treatment for Glioblastoma (GBM) using photothermal chemotherapy (PCT) with thermosensitive liposomes coencapsulated with TMZ16e and gold nanoparticles modified with anti-EphA3.
  • The thermosensitive liposomes were designed to release TMZ16e under infrared irradiation, allowing for targeted chemotherapy.
  • The study evaluates the safety and efficacy of this treatment in vitro and in vivo, with the goal of improving patient prognosis and quality of life.

Comparative Analysis & Findings

  • The prepared anti-EphA3-TMZ16e-GNPs-TSL had a particle size of 173.7±1.2 nm and were found to be non-toxic for the nasal mucosa.
  • In vitro cellular assays showed that the cytotoxicity in the anti-EphA3-TMZ16e-GNPs-TSL group was significantly higher 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, leading to increased tumor cell apoptosis and a median survival time of 47 days.

Implications and Future Directions

  • The targeted PCT system shows promise as a treatment strategy for GBM, offering a more precise and potent therapeutic intervention.
  • Further studies are needed to evaluate the long-term safety and efficacy of this treatment and to explore its potential for combination therapy with other treatments.
  • Future research could also investigate the use of this system for other types of cancer and explore ways to improve its stability and bioavailability.
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