Radiosensitizing Fe-Au nanocapsules (hybridosomes®) increase survival of GL261 brain tumor-bearing mice treated by radiotherapy
Résumé
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 combined therapies development (chemo-radiotherapy).
Mots clés
Glioblastoma
Nanoparticles
Hybridosomes®
Combined therapies
Radiotherapy
Chemotherapy
Mouse Models
MRI and Bioluminescence
BBB
Blood Brain Barrier GBM
Glioblastoma H®
Hybridosome® H(Fe)
Iron oxide Hybridosome® H(Fe Au)
Iron Oxide and Gold Hybridosome® IR Irradiation MRI
Magnetic Resonance Imaging NP
nanoparticle(s) NTA
Nanoparticle Tracking Analysis ROS
Reactive Oxygen Species SPION
iron oxide superparamagnetic nanoparticles TEM
Transmission Electron Microscopy Glioblastoma
Chemotherapy Mouse Models
Blood Brain Barrier
GBM
H®
Hybridosome®
H(Fe)
Iron oxide Hybridosome®
H(Fe
Au)
Iron Oxide and Gold Hybridosome®
IR
Irradiation
MRI
Magnetic Resonance Imaging
NP
nanoparticle(s)
NTA
Nanoparticle Tracking Analysis
ROS
Reactive Oxygen Species
SPION
iron oxide superparamagnetic nanoparticles
TEM
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Goubaud-2022-Radiosensitizing Fe-Au Nanocapsules_vSubmitted__NANO-0000102499_S.CHEVANCE.pdf (2.17 Mo)
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Goubault_1-s2.0-S1549963421001428-mmc1.pdf (1.06 Mo)
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