scholarly journals Overcoming Radiation Resistance by Iron-Platinum Metal Alloy Nanoparticles in Human Copper Transport 1-Overexpressing Cancer Cells via Mitochondrial Disturbance

2021 ◽  
Vol Volume 16 ◽  
pp. 2071-2085
Author(s):  
Tsung-Lin Tsai ◽  
Yu-Hsuan Lai ◽  
Helen H W Chen ◽  
Wu-Chou Su
2020 ◽  
Author(s):  
Tsung-Lin Tsai ◽  
Yu-Hsuan Lai ◽  
Helen H. W. Chen ◽  
Wu-Chou Su

Abstract Background Radiation therapy remains an important treatment modality in cancer therapy, however, resistance is a major problem for treatment failure. Elevated expression of glutathione (GSH) is known to associate with radiation resistance. We used GSH overexpressing small cell lung cancer cell lines, SR3A-13 and SR3A-14, established by transfection with γ-glutamylcysteine synthetase (γ-GCS) cDNA, as a model for investigating strategies of overcoming radiation resistance. These radiation-resistant cells exhibit upregulated human copper transporter 1 (hCtr1), which also transports cisplatin. This study was initiated to investigate the effect and the underlying mechanism of iron-platinum nanoparticles (FePt NPs) on radiation sensitization in cancer cells.Methods Uptakes of FePt NPs in these cells were studied by plasma optical emission spectrometry and transmission electron microscopy. Effects of the combination of FePt NPs and ionizing radiation (IR) were investigated by colony formation assay and animal experiment. Intracellular reactive oxygen species (ROS) were assessed by using fluorescent probes and imaged by a fluorescence-activated-cell-sorting caliber flow cytometer. Oxygen consumption rate (OCR) in mitochondria after FePt NP and IR treatment was investigated by a Seahoarse XF24 cell energy metabolism analyzer.Results These hCtr1-overexpressing cells exhibited elevated resistance to IR and the resistance could be overcome by FePt NPs via enhanced uptake of FePt NPs. Overexpression of hCtr1 was responsible for the increased uptake/transport of FePt NPs as demonstrated by using hCtr1-transfected parental SR3A (SR3A-hCtr1-WT) cells. Increased reactive oxygen species (ROS) and drastic mitochondrial damages with substantial reduction of oxygen consumption rate were observed in FePt NPs and IR-treated cells, indicating that structural and functional insults of mitochondria is the lethal mechanism of FePt NPs. Furthermore, FePt NPs also increased the efficacy of radiotherapy in mice bearing SR3A-hCtr1-WT-xenograft tumors.Conclusion These results suggest that FePt NPs can potentially be a novel strategy to improve radiotherapeutic efficacy in hCtr1-overexpressing cancer cells via enhanced uptake and mitochondria targeting.


2014 ◽  
Vol 2 (31) ◽  
pp. 12535 ◽  
Author(s):  
Nirmalya Moitra ◽  
Kazuyoshi Kanamori ◽  
Yumi H. Ikuhara ◽  
Xiang Gao ◽  
Yang Zhu ◽  
...  

The Analyst ◽  
2014 ◽  
Vol 139 (20) ◽  
pp. 5247-5253 ◽  
Author(s):  
Sergiy Patskovsky ◽  
Eric Bergeron ◽  
David Rioux ◽  
Mikaël Simard ◽  
Michel Meunier

We report a hyperspectral reflected light microscopy system for plasmonic nanoparticle (NP) imaging, and compare with a conventional darkfield method for spatial localization and spectroscopic identification of single Au, Ag and Au/Ag alloy NPs incubated with fixed human cancer cell preparations.


Nanomaterials ◽  
2022 ◽  
Vol 12 (2) ◽  
pp. 258
Author(s):  
Asit Kumar Panda ◽  
Murugan Keerthi ◽  
Rajalakshmi Sakthivel ◽  
Udesh Dhawan ◽  
Xinke Liu ◽  
...  

Hydrogen sulfide (H2S), an endogenous gasotransmitter, is produced in mammalian systems and is closely associated with pathological and physiological functions. Nevertheless, the complete conversion of H2S is still unpredictable owing to the limited number of sensors for accurate and quantitative detection of H2S in biological samples. In this study, we constructed a disposable electrochemical sensor based on PtNi alloy nanoparticles (PtNi NPs) for sensitive and specific in situ monitoring of H2S released by human breast cancer cells. PtNi alloy NPs with an average size of 5.6 nm were prepared by a simple hydrothermal approach. The conversion of different forms of sulfides (e.g., H2S, HS−, and S2−) under various physiological conditions hindered the direct detection of H2S in live cells. PtNi NPs catalyze the electrochemical oxidation of H2S in a neutral phosphate buffer (PB, pH 7.0). The PtNi-based sensing platform demonstrated a linear detection range of 0.013–1031 µM and the limit of detection was 0.004 µM (S/N = 3). Moreover, the PtNi sensor exhibited a sensitivity of 0.323 μA μM−1 cm−2. In addition, the stability, repeatability, reproducibility, and anti-interference ability of the PtNi sensor exhibited satisfactory results. The PtNi sensor was able to successfully quantify H2S in pond water, urine, and saliva samples. Finally, the biocompatible PtNi electrode was effectively employed for the real-time quantification of H2S released from breast cancer cells and mouse fibroblasts.


Author(s):  
G Negro ◽  
B Aschenbrenner ◽  
S Skvortsov ◽  
C Jimenez ◽  
U Ganswindt ◽  
...  

2019 ◽  
Vol 193 (1) ◽  
pp. 82 ◽  
Author(s):  
Matthias Müller ◽  
Sara Espinoza ◽  
Thomas Jüstel ◽  
Kathryn D. Held ◽  
R. Rox Anderson ◽  
...  

ACS Photonics ◽  
2019 ◽  
Vol 6 (3) ◽  
pp. 779-786 ◽  
Author(s):  
Shima Kadkhodazadeh ◽  
Ferry Anggoro Ardy Nugroho ◽  
Christoph Langhammer ◽  
Marco Beleggia ◽  
Jakob B. Wagner

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Al Tamimi ◽  
Sarmadia Ashraf ◽  
Tahir Abdulrehman ◽  
Aijaz Parray ◽  
Said A. Mansour ◽  
...  

Abstract Background Breast cancer is therapeutically very challenging to treat as it has the main four known genetic alterations, which result in the existence of several phenotypes leading to the difference in the mode of therapy and with poor outcome. Metallic nanoparticles of silver or copper have been studied previously as anticancer agents in breast cancer and other types of cancers. However, the anticancer effect of silver–copper alloy nanoparticles (AgCu-NP) is not studied in breast cancer. In this study, we aim to synthesize silver nanoparticles (Ag-NP), or copper nanoparticles (Cu-NP), and AgCu-NP and evaluate their toxicity in breast cancer and healthy breast cells. Results We synthesized sodium citrate and mercapto-propionic acid (MPA-3) capped water-soluble metallic nanoparticles of Ag-NP or Cu-NP and an alloy of three different combinations of AgCu-NP. High-resolution transmission electron microscopy characterization of nanoparticles revealed the spherical shape nanoparticles of varied sizes, furthermore dynamic light scattering characterization was performed, which investigated the hydrodynamic size and stability in phosphate buffer solution. Energy-dispersive X-ray spectroscopy (EDS) measurements were obtained from the transmission electron microscope to study the composition of alloy nanoparticles and the distribution pattern of silver and copper in the alloy nanoparticles. We measured the toxicity of nanoparticles to breast cancer MCF-7 cell line by MTT assay and compared the toxic effect with non-cancerous breast epithelial cells MCF-10A. Our data showed that Ag-NP or Cu-NP have no effect on cancer cells or healthy cells, except Ag-NP at 20 µg/ml were toxic to cancer cells. However, AgCu-NP were significantly toxic to MCF-7 cells at 10 µg/ml concentration, while as AgCu-NP have no toxic effect on healthy cells. Furthermore, we observed the cell death pathway by the apoptosis marker Annexin-V which showed non-significant results, while the exposure of AgCu-NP in MCF-7 cells leads to toxicity and also caused significant increase in MMP-9 level, which suggests the cell death may be associated with other pathways such as autophagy and oxidative stress related. Conclusion The data suggest that the AgCu-NP alloy imposes preferential toxicity in breast cancer MCF-7 cells and thus could be exploited as a new candidate for further anticancer investigation


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