Gold nanotriangles: scale up and X-ray radiosensitization effects in mice

Bhattarai, Shanta Raj; Derry, Paul J.; Aziz, Kathryn E.; Singh, Pankaj Kumar; Khoo, Allison; Chadha, Awalpreet S.; Liopo, Anton V.; Zubarev, Eugene R.; Krishnan, Sunil

doi:10.1039/c6nr08172j

Cited by 58 publications

(46 citation statements)

References 38 publications

(44 reference statements)

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“…injection did not [ 47 ]. In a recent study, 24 h after the injection of 2.7 mg/kg PEGylated NPRs (61.51 ± 2.91 nm) (57 μg per mouse) it was found that the nanoparticles presented the highest level of accumulation in the spleen, whereas the liver and intestine had the next highest concentrations [ 49 ]. Moreover, these PEGylated NPRs did not provoke significant biochemical or hematological differences between untreated control mice and nanoparticles-treated mice, which is in accordance to our results.…”

Section: Discussionmentioning

confidence: 99%

Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

et al. 2017

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BackgroundThe special physicochemical properties of gold nanoprisms make them very useful for biomedical applications including biosensing and cancer therapy. However, it is not clear how gold nanoprisms may affect cellular physiology including viability and other critical functions. We report a multiparametric investigation on the impact of gold-nanoprisms on mice and human, transformed and primary cells as well as tissue distribution and toxicity in vivo after parental injection.MethodsCellular uptake of the gold-nanoprisms (NPRs) and the most crucial parameters of cell fitness such as generation of reactive oxygen species (ROS), mitochondria membrane potential, cell morphology and apoptosis were systematically assayed in cells. Organ distribution and toxicity including inflammatory response were analysed in vivo in mice at 3 days or 4 months after parental administration.ResultsInternalized gold-nanoprisms have a significant impact in cell morphology, mitochondrial function and ROS production, which however do not affect the potential of cells to proliferate and form colonies. In vivo NPRs were only detected in spleen and liver at 3 days and 4 months after administration, which correlated with some changes in tissue architecture. However, the main serum biochemical markers of organ damage and inflammation (TNFα and IFNγ) remained unaltered even after 4 months. In addition, animals did not show any macroscopic sign of toxicity and remained healthy during all the study period.ConclusionOur data indicate that these gold-nanoprisms are neither cytotoxic nor cytostatic in transformed and primary cells, and suggest that extensive parameters should be analysed in different cell types to draw useful conclusions on nanomaterials safety. Moreover, although there is a tendency for the NPRs to accumulate in liver and spleen, there is no observable negative impact on animal health.Electronic supplementary materialThe online version of this article (10.1186/s12989-017-0222-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

et al. 2017

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“…Since GBM is considered as a radioresistant tumor [3] and most of the recurrence occurs in the radiotherapy field [4], radiosensitization of the tumor is an important target to improve the outcome in patients with GBM. Therefore, multiple radiosensitizing strategies are actively under development, including PI3K pathway inhibitors [5], DNA repair inhibitors [6], hyperthermia [7], aldehyde dehydrogenase inhibitors [8], and high atomic number (high-Z) metal nanoparticles (NPs) [9].…”

Section: Introductionmentioning

confidence: 99%

Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

et al. 2020

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Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.

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“…In subsequent attempts, GNPs are often coated with polyethylene glycol (“pegylated”) to decrease reticuloendothelial cell capture and conjugated to active cancer-specific targeting moieties to achieve favorable pharmacokinetics and durable localization to tumor cells 12 . Further experimentation using a variety of GNP shapes and sizes have shown differing rates of blood vessel extravasation and metabolic clearance 12 , 13 . Nanorods, for example, have been shown to offer superior intratumoral transport and distribution compared with nanospheres 14 .…”

Section: Introductionmentioning

confidence: 99%

Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles

Khoo

Cho

Reynoso

et al. 2017

Sci Rep

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Theoretical investigations suggest that gold nanoparticle (GNP)-mediated radiation dose enhancement and radiosensitization can be maximized when photons interact with gold, predominantly via photoelectric absorption. This makes ytterbium (Yb)-169, which emits photons with an average energy of 93 keV (just above the K-edge of gold), an ideal radioisotope for such purposes. This investigation tests the feasibility of tumor-specific prostate brachytherapy achievable with Yb-169 and actively targeted GNPs, using an external beam surrogate of Yb-169 created from an exotic filter material - erbium (Er) and a standard copper-filtered 250 kVp beam. The current in vitro study shows that treatment of prostate cancer cells with goserelin-conjugated gold nanorods (gGNRs) promotes gonadotropin releasing hormone receptor-mediated internalization and enhances radiosensitivity to both Er-filtered and standard 250 kVp beams, 14 and 10%, respectively. While the degree of GNP-mediated radiosensitization as seen from the in vitro study may be considered moderate, the current in vivo study shows that gGNR treatment plus Er-filtered x-ray irradiation is considerably more effective than radiation treatment alone (p < 0.0005), resulting in a striking reduction in tumor volume (50% smaller) 2 months following treatment. Overall, the current results provide strong evidence for the feasibility of tumor-specific prostate brachytherapy with Yb-169 and gGNRs.

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Gold nanotriangles: scale up and X-ray radiosensitization effects in mice

Cited by 58 publications

References 38 publications

Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

Multiparametric analysis of anti-proliferative and apoptotic effects of gold nanoprisms on mouse and human primary and transformed cells, biodistribution and toxicity in vivo

Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

Radiosensitization of Prostate Cancers In Vitro and In Vivo to Erbium-filtered Orthovoltage X-rays Using Actively Targeted Gold Nanoparticles

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