Cytotoxic effects of cytoplasmic-targeted and nuclear-targeted gold and silver nanoparticles in HSC-3 cells – A mechanistic study

Austin, Lauren A.; Ahmad, Samera; Kang, Bin; Rommel, Kathryn R; Mahmoud, Mahmoud Abdelbaky; Peek, Mary Elizabeth; El‐Sayed, Mostafa A.

doi:10.1016/j.tiv.2014.11.003

Cited by 30 publications

(20 citation statements)

References 41 publications

(52 reference statements)

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“…The reduction of total cell number by X-ray irradiation alone and when combined with AuNPs was apparently due to the induction of apoptosis, but not inhibition of cell proliferation. To the best of our knowledge, although there have been reports on localization-dependent cytotoxicity of AuNPs alone (9) and the chemosensitization effect of AuNPs (specifically, nuclear-targeted 30-nm AuNPs enhanced 5-fluorouracil drug efficacy in HSC-3 cells via regulation of the cell cycle) (10), this is the first report indicating a radiosensitization effect of AuNPs against human head and neck squamous cell carcinoma cells in vitro.…”

Section: Discussionmentioning

confidence: 93%

“…Although there have been numerous studies on radiosensitization using AuNPs in various cell lines (3), few studies have used human head and neck cancer cells. However, one study did indicate localization-dependent (extracellular, cytoplasmic and nuclear localization of AuNPs) cytotoxicity in human oral squamous cell carcinoma cells (9). Another study reported that AuNPs enhanced chemosensitization in human oral squamous cell carcinoma cells via cell cycle regulation (10).…”

Section: Introductionmentioning

confidence: 99%

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Gold nanoparticles enhance X‑ray irradiation‑induced apoptosis in head and neck squamous cell carcinoma in�vitro

et al. 2018

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Enhancing the antitumor effect of radiation, while reducing damage to organs, is a significant challenge in radiation therapy for head and neck malignancies. One promising radiosensitizer is gold. The present study aimed to determine whether gold nanoparticles (AuNPs) have the potential to enhance the effects of X-ray irradiation on head and neck cancer cells. The human head and neck carcinoma cell line HSC-3 was used. Total cell number and the levels of cell proliferation and apoptosis were compared between control cells and cells treated with 5-nm AuNPs alone at four concentrations (0.1, 0.4, 1.0 and 10.0 nM), X-ray irradiation alone at three doses (2, 4 and 8 Gy), or a combination of 4 Gy X-ray irradiation and 1.0 nM AuNPs. Analysis of variance and Tukey-Kramer testing were performed to compare the different groups. The total number of cells significantly decreased following 4 and 8 Gy X-ray irradiation, compared with in the control group (control vs. 4Gy, P=2.19x10-4 ; control vs. 8Gy, P=1.28x10-6). The combination of 4 Gy X-ray irradiation and 1.0 nM AuNPs significantly reduced the total number of cells compared with 4 Gy X-ray irradiation alone (P=2.95x10-4). Cell proliferation was not affected by AuNP treatment alone, 4 Gy X-ray irradiation alone or the combination of X-ray irradiation and AuNPs. The combination of 4 Gy irradiation and 1.0 nM AuNPs significantly increased the number of apoptotic cells compared with 4 Gy irradiation alone (P=0.0261). In conclusion, AuNPs combined with X-ray irradiation enhanced the cytotoxic effect on human head and neck cancer cells in vitro, through the induction of apoptosis, but not inhibition of cell proliferation.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Gold nanoparticles enhance X‑ray irradiation‑induced apoptosis in head and neck squamous cell carcinoma in�vitro

et al. 2018

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“…For SERS studies, the cells were seeded on glass coverslips in complete growth medium for 24 h to achieve a 40% final confluence before SERS study. The cells were then incubated with 0.05 nM PEG/RGD/NLS-functionalized AuNSs in supplemented DMEM cell culture medium for 24 h . Six hours before the SERS examination, the cell media (with AuNSs) were removed, and a 2.5 nM concentration of AuNRs suspended in supplemented medium was added to the cells to perform PPTT.…”

Section: Methodsmentioning

confidence: 99%

Simultaneous Time-Dependent Surface-Enhanced Raman Spectroscopy, Metabolomics, and Proteomics Reveal Cancer Cell Death Mechanisms Associated with Gold Nanorod Photothermal Therapy

et al. 2016

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In cancer plasmonic photothermal therapy (PPTT), plasmonic nanoparticles are used to convert light into localized heat, leading to cancer cell death. Among plasmonic nanoparticles, gold nanorods (AuNRs) with specific dimensions enabling them to absorb near-infrared laser light have been widely used. The detailed mechanism of PPTT therapy, however, still remains poorly understood. Typically, surface-enhanced Raman spectroscopy (SERS) has been used to detect time-dependent changes in the intensity of the vibration frequencies of molecules that appear or disappear during different cellular processes. A complete proven assignment of the molecular identity of these vibrations and their biological importance has not yet been accomplished. Mass spectrometry (MS) is a powerful technique that is able to accurately identify molecules in chemical mixtures by observing their m/z values and fragmentation patterns. Here, we complemented the study of changes in SERS spectra with MS-based metabolomics and proteomics to identify the chemical species responsible for the observed changes in SERS band intensities during PPTT. We observed an increase in intensity of the bands at around 1000, 1207, and 1580 cm, which were assigned in the literature to phenylalanine, albeit with dispute. Our metabolomics results showed increased levels of phenylalanine, its derivatives, and phenylalanine-containing peptides, providing evidence for more confidence in the SERS peak assignments. To better understand the mechanism of phenylalanine increase upon PPTT, we combined metabolomics and proteomics results through network analysis, which proved that phenylalanine metabolism was perturbed. Furthermore, several apoptosis pathways were activated via key proteins (e.g., HADHA and ACAT1), consistent with the proposed role of altered phenylalanine metabolism in inducing apoptosis. Our study shows that the integration of the SERS with MS-based metabolomics and proteomics can assist the assignment of signals in SERS spectra and further characterize the related molecular mechanisms of the cellular processes involved in PPTT.

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“…On the other hand, silver (Ag) is famous for its biocidal activity against broad spectrum of microbial and fungal species 15,16 , yet the human immune system is sensitive to the toxic effects rendered by free silver nanoparticles (Ag NPs) particularly at high concentrations 17,18 . Because of their small size and high mobility, Ag NPs can enter mammalian cells and undermine intracellular functions [19][20][21] . Therefore, restricting the mobility of Ag NPs is critical to clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Balancing the Osteogenic and Antibacterial Properties of Titanium by Codoping of Mg and Ag: An in Vitro and in Vivo Study

Zhao

Cao

Qin

et al. 2015

ACS Appl. Mater. Interfaces

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To simultaneously enhance the osteogenic and antibacterial properties of titanium, we introduced magnesium (Mg), silver (Ag), or both by using the plasma immersion ion implantation (PIII) technique, producing three PIII sample groups, namely, Mg-doped titanium (Mg-PIII), Ag-doped titanium (Ag-PIII), and Mg and Ag codoped titanium (Mg/Ag-PIII). The in vitro antibacterial efficacy of Mg/Ag-PIII group was about 7-10% higher than that of Ag-PIII. In vitro and in vivo results demonstrated that osteogenic property of Mg/Ag PIII group was better than that of Ag-PIII or Mg-PIII. It was believed that the galvanic effects between Mg and Ag NPs played a key role in facilitating the release of Mg but reducing the release of silver, answering for the selective performances of the Mg/Ag-PIII group over bacterial and mammalian cells. This study demonstrated that the integration of multiple functional elements could be realized by the dual-source PIII technique, and in this case, the antibacterial properties and osteogenic property of titanium could be balanced.

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Cytotoxic effects of cytoplasmic-targeted and nuclear-targeted gold and silver nanoparticles in HSC-3 cells – A mechanistic study

Cited by 30 publications

References 41 publications

Gold nanoparticles enhance X‑ray irradiation‑induced apoptosis in head and neck squamous cell carcinoma in�vitro

Gold nanoparticles enhance X‑ray irradiation‑induced apoptosis in head and neck squamous cell carcinoma in�vitro

Simultaneous Time-Dependent Surface-Enhanced Raman Spectroscopy, Metabolomics, and Proteomics Reveal Cancer Cell Death Mechanisms Associated with Gold Nanorod Photothermal Therapy

Balancing the Osteogenic and Antibacterial Properties of Titanium by Codoping of Mg and Ag: An in Vitro and in Vivo Study

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