Radiosensitization by gold nanoparticles: Will they ever make it to the clinic?

Cui, Lei; Her, Sohyoung; Borst, Gerben R.; Bristow, Robert G.; Jaffray, David A.; Allen, Christine

doi:10.1016/j.radonc.2017.07.007

Cited by 133 publications

(118 citation statements)

References 183 publications

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“…The differences in charge and coating of the NPs might also justify the effective dose enhancement induced by AuNP-Gd and AuNP-Gd-BBN. Our results are in agreement with other studies reported in the literature [5,26,28,32,33,63,64]. Overall, both AuNP-Gd and AuNP-Gd-BBN nanoplatforms have very promising properties as radiosensitizers.…”

Section: Discussionsupporting

confidence: 93%

Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

et al. 2020

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Gold nanoparticles (AuNPs) are interesting for the design of new cancer theranostic tools, mainly due to their biocompatibility, easy molecular vectorization, and good biological half-life. Herein, we report a gold nanoparticle platform as a bimodal imaging probe, capable of coordinating Gd3+ for Magnetic Resonance Imaging (MRI) and 67Ga3+ for Single Photon Emission Computed Tomography (SPECT) imaging. Our AuNPs carry a bombesin analogue with affinity towards the gastrin releasing peptide receptor (GRPr), overexpressed in a variety of human cancer cells, namely PC3 prostate cancer cells. The potential of these multimodal imaging nanoconstructs was thoroughly investigated by the assessment of their magnetic properties, in vitro cellular uptake, biodistribution, and radiosensitisation assays. The relaxometric properties predict a potential T1- and T2- MRI application. The promising in vitro cellular uptake of 67Ga/Gd-based bombesin containing particles was confirmed through biodistribution studies in tumor bearing mice, indicating their integrity and ability to target the GRPr. Radiosensitization studies revealed the therapeutic potential of the nanoparticles. Moreover, the DOTA chelating unit moiety versatility gives a high theranostic potential through the coordination of other therapeutically interesting radiometals. Altogether, our nanoparticles are interesting nanomaterial for theranostic application and as bimodal T1- and T2- MRI / SPECT imaging probes.

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Section: Discussionsupporting

confidence: 93%

Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

et al. 2020

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“…Due to some singular physico-chemical characteristics, AuNPs have also been studied for therapeutic and diagnostic purposes [25]. Since they are capable of elevated photoelectric absorption of radiation energy compared to soft tissues, these nanomaterials are recognised as excellent enhancers of radiotherapy [26]. In addition, gold nanoparticles are outstanding delivery platforms of cytotoxic drugs or therapeutic genes, which can ultimately be directed-rather selectively-into the microenvironment of the cancerous tissues, by exploiting the characteristic vascular abnormalities of solid tumours, often cited as enhanced permeability and retention effect (EPR) [27].…”

Section: Introductionmentioning

confidence: 99%

Core–shell nanoparticles suppress metastasis and modify the tumour-supportive activity of cancer-associated fibroblasts

et al. 2020

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Background: Although accumulating evidence suggests that the crosstalk between malignant cells and cancerassociated fibroblasts (CAFs) actively contributes to tumour growth and metastatic dissemination, therapeutic strategies targeting tumour stroma are still not common in the clinical practice. Metal-based nanomaterials have been shown to exert excellent cytotoxic and anti-cancerous activities, however, their effects on the reactive stroma have never been investigated in details. Thus, using feasible in vitro and in vivo systems to model tumour microenvironment, we tested whether the presence of gold, silver or gold-core silver-shell nanoparticles exerts anti-tumour and metastasis suppressing activities by influencing the tumour-supporting activity of stromal fibroblasts. Results: We found that the presence of gold-core silver-shell hybrid nanomaterials in the tumour microenvironment attenuated the tumour cell-promoting behaviour of CAFs, and this phenomenon led to a prominent attenuation of metastatic dissemination in vivo as well. Mechanistically, transcriptome analysis on tumour-promoting CAFs revealed that silver-based nanomaterials trigger expressional changes in genes related to cancer invasion and tumour metastasis. Conclusions: Here we report that metal nanoparticles can influence the cancer-promoting activity of tumour stroma by affecting the gene expressional and secretory profiles of stromal fibroblasts and thereby altering their intrinsic crosstalk with malignant cells. This potential of metal nanomaterials should be exploited in multimodal treatment approaches and translated into improved therapeutic outcomes.

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“…High-Z metal-based nanoparticles possess high X-ray photon capture cross-sections and are capable of increasing the production of secondary and Auger electrons, which in turn increases the generated reactive oxygen species (ROS) and enhances radiotherapy. 8,9 In addition to gold nanoparticles, which are the first and most studied nanoparticles and the enhancement effects of which have been demonstrated both in vitro and in vivo, [10][11][12] gadolinium-based nanoparticles (GdNPs) have also attracted substantial attention because of their high relaxation time and high atomic number (Z=64). [13][14][15][16] Ultra-small gadolinium oxide nanocrystals (GONs) are attractive GdNPs that possess a high density of Gd per contrastagent unit (200-400 atoms per particle).…”

Section: Introductionmentioning

confidence: 99%

<p>Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy</p>

Li¹,

Li²,

Jiang³

et al. 2019

IJN

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Background Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radio-sensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation. Method and materials GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation. Results GONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation. Conclusion This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation.

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Radiosensitization by gold nanoparticles: Will they ever make it to the clinic?

Cited by 133 publications

References 183 publications

Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

Dual Imaging Gold Nanoplatforms for Targeted Radiotheranostics

Core–shell nanoparticles suppress metastasis and modify the tumour-supportive activity of cancer-associated fibroblasts

<p>Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy</p>

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