The detrimental invasiveness of glioma cells controlled by gadolinium chelate-coated gold nanoparticles

Durand, Maxime; Lelièvre, Elodie; Chateau, Alicia; Berquand, Alexandre; Laurent, Gautier; Carl, Philippe; Roux, Stéphane; Chazée, Lise; Bazzi, Rana; Eghiaian, Frédéric; Jubréaux, Justine; Rondé, Philippe; Barberi‐Heyob, Muriel; Chastagner, Pascal; Devy, Jérôme; Pinel, Sophie

doi:10.1039/d0nr08936b

Cited by 9 publications

(7 citation statements)

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“…Recently, we have demonstrated on glioblastoma cells grown as monolayers that Au@DTDTPA(Gd) uptake induced a marked increase of the Young’s modulus measured by atomic force microscopy and a decreased number of protrusions, causing an increased cell stiffness and impaired cell motility. 16 In the present study, when U87 spheroids were treated by RT+NPs, the living escaped cells appeared unable to form the interconnected network and we assume that similar mechanisms were involved. Moreover, living escaped cells exhibited reduced metalloprotease activity in RT+NPs groups.…”

Section: Discussionmentioning

confidence: 51%

“…Au@DTDTPA(Gd) nanoparticles were synthesized and characterized as previously described in our published work. 16 For a typical preparation of gold nanoparticles, HAuCl 4 ·3H 2 O (200 mg, 51×10 −5 mol) was placed in a 250 mL round-bottom flask and was dissolved with methanol (60 mL). In another flask, DTDTPA (256 mg, 50×10 −5 mol), water (40 mL) and acetic acid (2 mL) were mixed.…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate the “fractionation effect”, we compared 3 schedules of irradiation at the total dose of 10 Gy: between T8 and T12, U87 spheroids were irradiated either at 10 Gy-monodose, with 2 fractions of 5 Gy (2 X 5 Gy) or with 5 fractions of 2 Gy (5 X 2 Gy) and untreated or treated U87 spheroids were recovered at T13. Conventional 3D invasion assays were performed and analysed as previously described, 16 ( Supplementary Methods 2 ). Briefly, each spheroid was placed into individual well of 96-well plate and then embedded with 100 µL of a mix of Matrigel ® and hyaluronic acid (100 µg/mL).…”

Section: Methodsmentioning

confidence: 99%

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Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma

Durand¹,

Chateau²,

Jubréaux³

et al. 2023

IJN

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Purpose This study aimed to evaluate the radiosensitizing potential of Au@DTDTPA(Gd) nanoparticles when combined with conventional external X-ray irradiation (RT) to treat GBM. Methods Complementary biological models based on U87 spheroids including conventional 3D invasion assay, organotypic brain slice cultures, chronic cranial window model were implemented to investigate the impact of RT treatments (10 Gy single dose; 5×2 Gy or 2×5 Gy) combined with Au@DTDTPA(Gd) nanoparticles on tumor progression. The main tumor mass and its infiltrative area were analyzed. This work focused on the invading cancer cells after irradiation and their viability, aggressiveness, and recurrence potential were assessed using mitotic catastrophe quantification, MMP secretion analysis and neurosphere assays, respectively. Results In vitro clonogenic assays showed that Au@DTDTPA(Gd) nanoparticles exerted a radiosensitizing effect on U87 cells, and in vivo experiments suggested a benefit of the combined treatment “RT 2×5 Gy + Au@DTDTPA(Gd)” compared to RT alone. Invasion assays revealed that invasion distance tended to increase after irradiation alone, while the combined treatments were able to significantly reduce tumor invasion. Monitoring of U87-GFP tumor progression using organotypic cultures or intracerebral grafts confirmed the anti-invasive effect of Au@DTDTPA(Gd) on irradiated spheroids. Most importantly, the combination of Au@DTDTPA(Gd) with irradiation drastically reduced the number, the viability and the aggressiveness of tumor cells able to escape from U87 spheroids. Notably, the combined treatments significantly reduced the proportion of escaped cells with stem-like features that could cause recurrence. Conclusion Combining Au@DTDTPA(Gd) nanoparticles and X-ray radiotherapy appears as an attractive therapeutic strategy to decrease number, viability and aggressiveness of tumor cells that escape and can invade the surrounding brain parenchyma. Hence, Au@DTDTPA(Gd)-enhanced radiotherapy opens up interesting perspectives for glioblastoma treatment.

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Section: Discussionmentioning

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma

Durand¹,

Chateau²,

Jubréaux³

et al. 2023

IJN

Self Cite

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“…Glioblastoma stem cells, which are extremely invasive, aggressive, and therapy-resistant, make up the glioma cells. They are thus distinguished by an invasive phenotype with strong migratory potential [ 94 ]. As a result, it is claimed that encapsulating various treatments into polymeric micelles will increase drug transport across the BBB.…”

Section: General Issues and Status Quo Of Polymeric Micellesmentioning

confidence: 99%

Polymeric Micellar Systems—A Special Emphasis on “Smart” Drug Delivery

Neguț

Biţă

2023

Pharmaceutics

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Concurrent developments in anticancer nanotechnological treatments have been observed as the burden of cancer increases every year. The 21st century has seen a transformation in the study of medicine thanks to the advancement in the field of material science and nanomedicine. Improved drug delivery systems with proven efficacy and fewer side effects have been made possible. Nanoformulations with varied functions are being created using lipids, polymers, and inorganic and peptide-based nanomedicines. Therefore, thorough knowledge of these intelligent nanomedicines is crucial for developing very promising drug delivery systems. Polymeric micelles are often simple to make and have high solubilization characteristics; as a result, they seem to be a promising alternative to other nanosystems. Even though recent studies have provided an overview of polymeric micelles, here we included a discussion on the “intelligent” drug delivery from these systems. We also summarized the state-of-the-art and the most recent developments of polymeric micellar systems with respect to cancer treatments. Additionally, we gave significant attention to the clinical translation potential of polymeric micellar systems in the treatment of various cancers.

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“…Au@DTDTPA(Gd) nanoparticles affected the intrinsic biomechanical properties of U251 glioma cells, such as cell stiffness, adhesion, and generated traction forces, and significantly reduced the formation of protrusions, thus, exerting an inhibitory effect on their migration capacities. The results showed that the Au@DTDTPA(Gd) nanoparticles could have great interest for the therapeutic management of astrocytic tumors, not only as a radio-enhancing agent but also by reducing the invasive potential of glioma cells [115].…”

Section: Applications In Cancer Treatmentmentioning

confidence: 99%

Consolidation of Gold and Gadolinium Nanoparticles: An Extra Step towards Improving Cancer Imaging and Therapy

Kouri

Polychronidou

Loukas

et al. 2023

JNT

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The multifactorial nature of cancer still classifies the disease as one of the leading causes of death worldwide. Modern medical sciences are following an interdisciplinary approach that has been fueled by the nanoscale revolution of the past years. The exploitation of high-Z materials, in combination with ionizing or non-ionizing radiation, promises to overcome restrictions in medical imaging and to augment the efficacy of current therapeutic modalities. Gold nanoparticles (AuNPs) have proven their value among the scientific community in various therapeutic and diagnostic techniques. However, the high level of multiparametric demands of AuNP experiments in combination with their biocompatibility and cytotoxicity levels remain crucial issues. Gadolinium NPs (GdNPs), have presented high biocompatibility, low cytotoxicity, and excellent hemocompatibility, and have been utilized in MRI-guided radiotherapy, photodynamic and photothermal therapy, etc. Τhe utilization of gadolinium bound to AuNPs may be a promising alternative that would reduce phenomena, such as toxicity, aggregation, etc., and could create a multimodal in vivo contrast and therapeutic agent. This review highlights multi-functionalization strategies against cancer where gold and gadolinium NPs are implicated. Their experimental applications and limitations of the past 5 years will be analyzed in the hope of enlightening the benefits and drawbacks of their proper combination.

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The detrimental invasiveness of glioma cells controlled by gadolinium chelate-coated gold nanoparticles

Abstract: Glioblastoma are characterized by an invasive phenotype, which is thought to be responsible for recurrences and the short overall survival of patients. In last decade, the promising potential of ultrasmall...

Cited by 9 publications

References 54 publications

Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma

Radiosensitization with Gadolinium Chelate-Coated Gold Nanoparticles Prevents Aggressiveness and Invasiveness in Glioblastoma

Polymeric Micellar Systems—A Special Emphasis on “Smart” Drug Delivery

Consolidation of Gold and Gadolinium Nanoparticles: An Extra Step towards Improving Cancer Imaging and Therapy

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