Gadolinium-Based Nanoparticles Can Overcome the Radioresistance of Head and Neck Squamous Cell Carcinoma Through the Induction of Autophagy

Abstract

Radiation therapy is a mainstay in the therapeutic management of Head and Neck Squamous Cell Carcinoma (HNSCC). Despite significant progress in this field, radioresistance still accounts for most treatment failures. Gadolinium-based nanoparticles (GBNs) have shown great promises as radiosensitizers but the underlying sensitizing mechanism is still largely unknown with regards to the disparities obtained in in vitro studies. In this study, we show that a new formulation of GBNs, AGuIX®, can radiosensitize HNSCC after cell uptake and further accumulation in lysosomes. Although radiation alone triggered late apoptosis and mitochondrial impairment, the pre-treatment with GBNs led to complex DNA damage and a specific increase of autophagic cell death. In addition, a significant radio-enhancement effect was obtained after the pre-conditioning of cells with a glutathione inhibitor before GBNs treatment and radiation exposure. Overall, our results provide additional information on the radio-enhancing properties of GBNs in the management of radioresistant HNSCC.

Gadolinium Oxide Nanoparticles Induce Toxicity in Human Endothelial HUVECs via Lipid Peroxidation, Mitochondrial Dysfunction and Autophagy Modulation

“…NPs based on rare-earth elements—including those of gadolinium, cerium, neodymium—have been reported to induce autophagy in human macrophage THP-1 cells [ 63 ], in two human glioblastoma cells ( U -87 MG and Mo59 K) [ 64 ] and in the cells of head and neck squamous cell carcinoma (HNSCC) [ 65 ]. Recently, gadolinium compound has also been reported to induce autophagy in the Mediterranean mussel Mytilus galloprovincialis [ 66 ].…”

AGuIX® from bench to bedside—Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

“…A recent study in radioresistant head and neck squamous cell carcinoma (HNSCC) SQ20B cells aimed to understand the radiosensitizing mechanisms in presence of AGuIX NPs. 61 Using 250 kV X-Rays, a surviving fraction at 4 Gy of 1.382 was obtained with an enhanced biological factor of 1.3 (incubation of cells at 0.8 mM in gadolinium). According to a previous study on U87MG glioblastoma cells, 58 AGuIX NPs are shown to principally localize in lysosomes with no particles detected in the nucleus.…”

Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy

“…It is a nonapoptotic form of programmed cell death caused by overactivated autophagy (Booth et al, 2019;Zhu et al, 2020). Anticancer treatment induces robust autophagy of cancer cells to self-digestion until death (Simonet et al, 2020;Ganesher et al, 2020). Many natural compounds and synthetic agents exhibit their anticancer effects through triggering autophagic cell death (Law et al, 2017;Xu et al, 2019;Kiruthiga et al, 2020;Pellerito et al, 2020).…”