Radiosensitizing Fe-Au nanocapsules (hybridosomes®) increase survival of GL261 brain tumor-bearing mice treated by radiotherapy

• Published in: Nanomedicine Vol. 40; p. 102499
• Main Authors: Goubault, Clément, Jarry, Ulrich, Bostoën, Mégane, Éliat, Pierre-Antoine, Kahn, Myrtil L., Pedeux, Rémy, Guillaudeux, Thierry, Gauffre, Fabienne, Chevance, Soizic
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2022; Elsevier
• Subjects: Animals; Biotechnology; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; Brain Neoplasms - radiotherapy; Cancer; Cell Line, Tumor; Chemical Sciences; Chemotherapy; Combined therapies; Glioblastoma; Glioblastoma - drug therapy; Glioblastoma - radiotherapy; Gold - therapeutic use; Hybridosomes; Life Sciences; Medication; Medicinal Chemistry; Metal Nanoparticles - therapeutic use; Mice; Mouse models; MRI and bioluminescence; Nanocapsules - therapeutic use; Nanoparticles; Pharmaceutical sciences; Radiotherapy; NP; MRI and bioluminescence; BBB; H(Fe); MRI; Glioblastoma; H; IR; Radiotherapy; Hybridosomes; Nanoparticles; Chemotherapy; GBM; Mouse models; H(Fe;Au); ROS; Combined therapies; NTA; SPION; TEM; Iron oxide Hybridosome; nanoparticle(s); Reactive Oxygen Species; Magnetic Resonance Imaging NP; Hybridosome® H(Fe); Glioblastoma H; Reactive Oxygen Species SPION; Au; nanoparticle(s) NTA; Iron Oxide and Gold Hybridosome® IR Irradiation MRI; Nanoparticle Tracking Analysis ROS; Nanoparticle Tracking Analysis; H(Fe; Hybridosome; Blood Brain Barrier; Iron oxide Hybridosome® H(Fe Au); iron oxide superparamagnetic nanoparticles TEM; Iron Oxide and Gold Hybridosome; Mouse Models; Magnetic Resonance Imaging; Transmission Electron Microscopy Glioblastoma; MRI and Bioluminescence; Chemotherapy Mouse Models; Irradiation; Blood Brain Barrier GBM; iron oxide superparamagnetic nanoparticles
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2021.102499

Glioblastoma remains a cancer for which the effectiveness of treatments has shown little improvement over the last decades. For this pathology, multiple therapies combining resection, chemotherapy and radiotherapy remain the norm. In this context, the use of high-Z nanoparticles such as gold or hafnium to potentiate radiotherapy is attracting more and more attention. Here, we evaluate the potentiating effect of hollow shells made of gold and iron oxide nanoparticles (hybridosomes®) on the radiotherapy of glioblastoma, using murine GL261-Luc+ brain tumor model. While iron oxide seems to have no beneficial effect for radiotherapy, we observe a real effect of gold nanoparticles—despite their low amount—with a median survival increase of almost 20% compared to radiotherapy only and even 33% compared to the control group. Cellular and in vivo studies show that a molecule of interest nano-precipitated in the core of the hybridosomes® is released and internalized by the surrounding brain cells. Finally, in vivo studies show that hybridosomes® injected intra-tumorally are still present in the vicinity of the brain tumor more than 5 days after injection (duration of the Stupp protocol's radiation treatment). Interestingly, one mouse treated with radiotherapy in the presence of gold-containing hybridosomes® survived 78 days. Monitoring of the tumoral growth of this long-term survivor using both MRI and bioluminescence revealed a decrease of the tumor size after treatment. These very encouraging results are a proof-of-concept that hybridosomes® are really effective tools for the development of combined therapies (chemo-radiotherapy). Legend: Intratumoral injection of iron oxide–gold nanocapsules (hybridosomes®) with radiotherapy increases the survival of brain tumor-bearing mice. The bioluminescence can be monitored as the tumoral cells express luciferase. [Display omitted]