Surface functionalization of gold nanoclusters with arginine: a trade-off between microtumor uptake and radiotherapy enhancement

Broekgaarden, Mans; Porret, Estelle; Musnier, Benjamin; Chovelon, Benoît; Ravelet, Corinne; Sancey, Lucie; Elleaume, Hélène; Hainaut, Pierre; Coll, Jean‐Luc; Guével, Xavier Le

doi:10.1039/d0nr01138j

Cited by 32 publications

(28 citation statements)

References 30 publications

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“…[ 25,57,58 ] Moreover, 3D microtumor models are more accurate in predicting in vivo radiotherapy outcomes compared to conventional 2D cultures, as we previously discussed. [ 59 ]…”

Section: Resultsmentioning

confidence: 99%

“…[25,57,58] Moreover, 3D microtumor models are more accurate in predicting in vivo radiotherapy outcomes compared to conventional 2D cultures, as we previously discussed. [59] Two glioblastoma spheroid models were established from two radioresistant glioblastoma cell lines: rat F98 [60,61] and human U-87 MG. [62,63] The toxicity of the LaF 3 :Ce nanoscintillators was investigated using dose-escalation studies by assessing the size and viability of the spheroids after 24 h of exposure. In F98 spheroids, the IC 50 of the LaF 3 :Ce nanoscintillators was 2.9 ± 0.1 mg mL −1 (Figure 3A,B), with no notable decrease in viability observed at concentrations below 1.0 mg mL −1 LaF 3 :Ce.…”

Section: Laf 3 :Ce Are Well-tolerated Up To 1 Mg ML −1 In Glioblastommentioning

confidence: 99%

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Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

et al. 2020

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To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down-convert X-rays into photons with energies ranging from UV to near-infrared. During radiotherapy, these scintillating properties amplify radiation-induced damage by UV-C emission or photodynamic effects. Additionally, nanoscintillators that contain high-Z elements are likely to induce another, currently unexplored effect: radiation dose-enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X-rays by high-Z elements compared to tissues, resulting in increased production of tissue-damaging photo-and Auger electrons. In this study, Geant4 simulations reveal that rare-earth composite LaF 3 :Ce nanoscintillators effectively generate photo-and Auger-electrons upon orthovoltage X-rays. 3D spatially resolved X-ray fluorescence microtomography shows that LaF 3 :Ce highly concentrates in microtumors and enhances radiotherapy in an X-ray energy-dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF 3 :Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose-enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers.

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“…[ 25,57,58 ] Moreover, 3D microtumor models are more accurate in predicting in vivo radiotherapy outcomes compared to conventional 2D cultures, as we previously discussed. [ 59 ]…”

Section: Resultsmentioning

confidence: 99%

Section: Laf 3 :Ce Are Well-tolerated Up To 1 Mg ML −1 In Glioblastommentioning

confidence: 99%

Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

et al. 2020

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“…Moreover, compared to GSH-protected Au NCs, poly-R conjugated ones exhibited higher quantum yields and prolonged luminescence lifetimes [59]. The potential effectiveness of cationic arginine-stabilized Au NCs (AuSG-2Arg) as diagnostic probes was investigated in cancerous cells lines by Broekgaarden et al The study confirmed that, despite a limited radiotherapeutic potential, AuSG-2Arg were more efficient diagnostic agents, compared to GSH-Au analogs, thanks to their enhanced uptake in glioblastoma models and increased emission intensity at 670 nm [60].…”

Section: Peptidesmentioning

confidence: 99%

Photoluminescent nanocluster-based probes for bioimaging applications

Bergamaschi

Metrangolo

Dichiarante

2022

Photochem Photobiol Sci

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In the continuous search for versatile and better performing probes for optical bioimaging and biosensing applications, many research efforts have focused on the design and optimization of photoluminescent metal nanoclusters. They consist of a metal core composed by a small number of atoms (diameter < 2-3 nm), usually coated by a shell of stabilizing ligands of different nature, and are characterized by molecule-like quantization of electronic states, resulting in discrete and tunable optical transitions in the UV-Vis and NIR spectral regions. Recent advances in their size-selective synthesis and tailored surface functionalization have allowed the effective combination of nanoclusters and biologically relevant molecules into hybrid platforms, that hold a large potential for bioimaging purposes, as well as for the detection and tracking of specific markers of biological processes or diseases. Here, we will present an overview of the latest combined imaging or sensing nanocluster-based systems reported in the literature, classified according to the different families of coating ligands (namely, peptides, proteins, nucleic acids, and biocompatible polymers), highlighting for each of them the possible applications in the biomedical field.

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“…In the literature, the most frequently reported GBM spheroids comprise only one human or one mouse cell line and are used to test the tumor penetration ability and cytotoxic activity of novel therapies, including cutting-edge nanosystem-based therapies. For instance, in a recent work, Broekgaarden et al used human derived U87MG spheroids and mouse derived F98 spheroids to test the tumor penetration and radiotherapy effectiveness of surfacefunctionalized gold nanoparticles (Broekgaarden et al, 2020). While these models are advantageous when compared with monolayered cell cultures, they still lack relevant TME elements, and do not mimic perivascular regions.…”

Section: Spherical Models-"free" or Matrix-supported Spheroidsmentioning

confidence: 99%

Glioblastoma Vasculature: From its Critical Role in Tumor Survival to Relevant in Vitro Modelling

Pacheco

Martins

Monteiro

et al. 2022

Front. Drug. Deliv.

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Biochemical and biophysical cues governing glioblastoma (GBM) progression are complex and dynamic. Tumor blood vessels, often recognized only by their transport functions, are more deeply involved in this process. Vessels are involved in tumor immune evasion, matrix alterations and stem cell stimulation, contributing for tumor treatment resistance and patients’ poor survival. Given blood vessel complex and dynamic nature, they are hardly represented in conventional GBM monolayered in vitro models. However, other in vitro approaches, such as three-dimensional (3D) models, incorporating extracellular matrix (ECM), malignant and stromal cells, and promoting their communication, can resemble neovascularization, growing blood vessels in a tumor-like microenvironment. These models mimic GBM physiological architecture and key biochemical and biophysical environments, allowing the investigation of the impact of vascularization in tumor progression. For researchers in neuro-oncology field, 3D vascularized GBM models are of great interest. They are promising tools to evaluate individual driven neovascularization and identify mediators involved in those processes. Moreover, they may be used to test potential anti-GBM therapies targeting blood vessels or influenced by them. This review will discuss the significance of blood vessels in GBM and review novel 3D pre-clinical vascular models.

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Surface functionalization of gold nanoclusters with arginine: a trade-off between microtumor uptake and radiotherapy enhancement

Abstract: Gold nanoclusters (AuNC) have strong potential for cancer imaging and therapy. We demonstrate that optimizing the surface chemistry of AuNCs for increased tumor uptake can significantly affect its potential to augment radiotherapy outcomes.

Cited by 32 publications

References 30 publications

Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

Photoluminescent nanocluster-based probes for bioimaging applications

Glioblastoma Vasculature: From its Critical Role in Tumor Survival to Relevant in Vitro Modelling

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