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Gold nanoparticles as a potent radiosensitizer in neutron therapy.

ABSTRACT: The purpose of this study was to investigate the potential of gold nanoparticles as radiosensitizer for use in neutron therapy against hepatocellular carcinoma. The hepatocellular carcinoma cells lines Huh7 and HepG2 were irradiated with ? and neutron radiation in the presence or absence of gold nanoparticles. Effects were evaluated by transmission electron microscopy, cell survival, cell cycle, DNA damage, migration, and invasiveness. Gold nanoparticles significantly enhanced the radiosensitivity of Huh7 and HepG2 cells to ?-rays by 1.41- and 1.16-fold, respectively, and by 1.80- and 1.35-fold to neutron radiation, which has high linear energy transfer. Accordingly, exposure to neutron radiation in the presence of gold nanoparticles induced cell cycle arrest, DNA damage, and cell death to a significantly higher extent, and suppressed cell migration and invasiveness more robustly. These effects are presumably due to the ability of gold nanoparticles to amplify the effective dose from neutron radiation more efficiently. The data suggest that gold nanoparticles may be clinically useful in combination therapy against hepatocellular carcinoma by enhancing the toxicity of radiation with high linear energy transfer.

SUBMITTER: Kim EH

PROVIDER: S-EPMC5762518 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Gold nanoparticles as a potent radiosensitizer in neutron therapy.

Kim Eun Ho EH Kim Mi-Sook MS Song Hyo Sook HS Yoo Seung Hoon SH Sai Sei S Chung Kwangzoo K Sung Jiwon J Jeong Youn Kyoung YK Jo YunHui Y Yoon Myonggeun M

Oncotarget 20170803 68

The purpose of this study was to investigate the potential of gold nanoparticles as radiosensitizer for use in neutron therapy against hepatocellular carcinoma. The hepatocellular carcinoma cells lines Huh7 and HepG2 were irradiated with γ and neutron radiation in the presence or absence of gold nanoparticles. Effects were evaluated by transmission electron microscopy, cell survival, cell cycle, DNA damage, migration, and invasiveness. Gold nanoparticles significantly enhanced the radiosensitivi ...[more]

PMID: 29348833

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Project description:Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]-) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ?-potential of -18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]- could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]-. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

Project description:PurposeWe investigated the dose enhancement and internalization of gold nanoparticles (AuNPs) used as a radiosensitizer agent for rotational radiotherapy of breast cancer using a kilovoltage (kV) X-ray beam.MethodsHuman breast cancer cells MDA-MB-231 were incubated with or without 100 μg/mL (4.87 nM) or 200 μg/mL (9.74 nM) 15 nm AuNPs and irradiated with 100 kV, 190 kV, or 6 MV X-rays. To assess the toxicity of the AuNPs, we performed a Sulforhodamine B assay. Using atomic absorption spectroscopy, scanning electron microscopy, transmission electron microscopy, and time-lapse optical microscopy (rate of 2 frames per minute), we carried out a quantitative assessment of the amount of gold internalized by MDA-MB-231 cells and a characterization of the static and dynamical aspects of this internalization process.ResultsNo effect of AuNPs alone was shown on cell viability. Time-lapse optical microscopy showed for the first time AuNPs cellular uptake and the dynamics of AuNPs internalization. Electron microscopy demonstrated AuNPs localization in endosomal vesicles, preferentially in the perinuclear region. After irradiation at doses up to 2 Gy, cell survival fraction curves showed increased mortality with AuNPs, with respect to irradiation without AuNPs. The highest effect of radioenhancement by AuNPs (at 9.74 nM AuNPs concentration) was observed at 190 kV showing a dose enhancement factor of 1.33 ± 0.06 (1.34 ± 0.02 at 100 kV), while at 6 MV it was 1.14 ± 0.06.ConclusionsThe observed radio-sensitization effect is promising for future radio-enhanced kV radiotherapy of breast cancer and quantitatively in the order of previous observations for 15 nm AuNPs. These results of a significant dose enhancement were obtained at 15 nm AuNPs concentration as low as several nanomolar units, at dose levels typical of a single dose fraction in a radiotherapy session. Dynamical behavior of the 3D spatial distribution of 15 nm AuNPs outside the nucleus of single breast cancer cell was observed, with possible implications for future models of AuNPs sensitization.

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Gold nanoparticles as a potent radiosensitizer in neutron therapy.

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Gold nanoparticles as a potent radiosensitizer in neutron therapy.

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