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

ABSTRACT: In the past decade, there has been considerable interest in radiosensitization using gold nanoparticles that accumulate specifically in cancerous tissue while sparing normal tissues. Despite this interest, it remains unclear which nanoparticle morphologies, cellular uptake, or cytoplasmic distribution elicit optimal radiosensitization. We introduce gold nanotriangles (AuNTs) as a possible X-ray radiotherapy sensitizer. In this study, we first explored a large-scale synthetic method for the production of high quality monodisperse AuNTs. Second, we conducted in vitro and in vivo experiments to evaluate the effect of PEGylated AuNTs (pAuNTs) on cellular uptake, cytotoxicity, bio-distribution, and radiosensitization on radiation-resistant human Glioblastoma Multiforme (GBM) cells. Our results suggest that the new scale up synthesis methodology consistently produced high quality AuNTs and pAuNTs which had nonspecific cellular uptake without any obvious cytotoxicity and exhibited excellent radiosensitization.

SUBMITTER: Bhattarai SR

PROVIDER: S-EPMC6091862 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Bhattarai S R SR Derry P J PJ Aziz K K Singh P K PK Khoo A M AM Chadha A S AS Liopo A A Zubarev E R ER Krishnan S S

Nanoscale 20170401 16

In the past decade, there has been considerable interest in radiosensitization using gold nanoparticles that accumulate specifically in cancerous tissue while sparing normal tissues. Despite this interest, it remains unclear which nanoparticle morphologies, cellular uptake, or cytoplasmic distribution elicit optimal radiosensitization. We introduce gold nanotriangles (AuNTs) as a possible X-ray radiotherapy sensitizer. In this study, we first explored a large-scale synthetic method for the produ ...[more]

PMID: 28134383

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Project description:The number of proton therapy facilities and the clinical usage of high energy proton beams for cancer treatment has substantially increased over the last decade. This is mainly due to the superior dose distribution of proton beams resulting in a reduction of side effects and a lower integral dose compared to conventional X-ray radiotherapy. More recently, the usage of metallic nanoparticles as radiosensitizers to enhance radiotherapy is receiving growing attention. While this strategy was originally intended for X-ray radiotherapy, there is currently a small number of experimental studies indicating promising results for proton therapy. However, most of these studies used low proton energies, which are less applicable to clinical practice; and very small gold nanoparticles (AuNPs). Therefore, this proof of principle study evaluates the radiosensitization effect of larger AuNPs in combination with a 200 MeV proton beam. CHO-K1 cells were exposed to a concentration of 10 μg/ml of 50 nm AuNPs for 4 hours before irradiation with a clinical proton beam at NRF iThemba LABS. AuNP internalization was confirmed by inductively coupled mass spectrometry and transmission electron microscopy, showing a random distribution of AuNPs throughout the cytoplasm of the cells and even some close localization to the nuclear membrane. The combined exposure to AuNPs and protons resulted in an increase in cell killing, which was 27.1% at 2 Gy and 43.8% at 6 Gy, compared to proton irradiation alone, illustrating the radiosensitizing potential of AuNPs. Additionally, cells were irradiated at different positions along the proton depth-dose curve to investigate the LET-dependence of AuNP radiosensitization. An increase in cytogenetic damage was observed at all depths for the combined treatment compared to protons alone, but no incremental increase with LET could be determined. In conclusion, this study confirms the potential of 50 nm AuNPs to increase the therapeutic efficacy of proton therapy.

Dataset Information

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

Publications

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

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