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Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages.

ABSTRACT: Recently, we have shown that targeting the cancer cell nucleus with solid gold nanospheres, using a cancer cell penetrating/pro-apoptotic peptide (RGD) and a nuclear localization sequence peptide (NLS), inhibits cell division, thus leading to apoptosis. In the present work, flow cytometric analysis revealed an increase in cell death, via apoptosis and necrosis, in HSC cells upon treatment with peptide-conjugated hollow gold nanocages, compared to those treated with the peptide-conjugated solid gold nanospheres. This is consistent with a G0/G1 phase accumulation, S phase depletion, and G2/M phase depletion, as well as reduced ATP levels. Here, we investigate the possible causes for the observed enhanced cell death with the use of confocal microscopy. The fluorescence images of HSC cells treated with gold nanocages indicate the presence of reactive oxygen species, known to cause apoptosis. The formation of reactive oxygen species observed is consistent with a mechanism involving the oxidation of metallic silver on the inner cavity of the nanocage (inherent to the synthesis of the gold nanocages) to silver oxide. This oxidation is confirmed by an observed redshift in the surface plasmon resonance of the gold nanocages in cell culture medium. The silver oxide, a semiconductor known to photochemically generate hydroxyl radicals, a form of reactive oxygen species, is proposed as a mechanism for the enhanced cell death caused by gold nanocages. Thus, the enhanced cell death, via apoptosis and necrosis, observed with peptide-conjugated hollow gold nanocage-treated cells is considered to be a result of the metallic composition (silver remaining on the inner cavity) of the nanocage.

SUBMITTER: Mackey MA

PROVIDER: S-EPMC3910495 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages.

Mackey Megan A MA Saira Farhat F Mahmoud Mahmoud A MA El-Sayed Mostafa A MA

Bioconjugate chemistry 20130610 6

Recently, we have shown that targeting the cancer cell nucleus with solid gold nanospheres, using a cancer cell penetrating/pro-apoptotic peptide (RGD) and a nuclear localization sequence peptide (NLS), inhibits cell division, thus leading to apoptosis. In the present work, flow cytometric analysis revealed an increase in cell death, via apoptosis and necrosis, in HSC cells upon treatment with peptide-conjugated hollow gold nanocages, compared to those treated with the peptide-conjugated solid g ...[more]

PMID: 23777334

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Project description:Purpose To determine if combretastatin A-4 phosphate disodium (CA4P) can enhance the tumor uptake of doxorubicin (Dox)-loaded, polyethylene glycol (PEG)-coated hollow gold nanospheres (HAuNS) mixed with ethiodized oil for improved photothermal ablation (PTA)-chemoembolization therapy (CET) of hepatocellular carcinoma (HCC) in rats. Materials and Methods Animal experiments were approved by the institutional animal care and use committee and performed from February 2014 to April 2015. Male Sprague-Dawley rats (n = 45; age, 12 weeks) were inoculated with N1S1 HCC cells in the liver, and 8 days later, were randomly divided into two groups of 10 rats. Group 1 rats received intrahepatic arterial injection of PEG-HAuNS and ethiodized oil alone; group 2 received pretreatment with CA4P and injection of PEG-HAuNS and ethiodized oil 5 minutes later. The gold content of tumor and liver tissue at 1 hour or 24 hours after injection was quantified by using neutron activation analysis (n = 5 per time point). Five rats received pretreatment CA4P, PEG-copper 64-HAuNS, and ethiodized oil and underwent micro-positron emission tomography (PET)/computed tomography (CT). In a separate study, three groups of six rats with HCC were injected with saline solution (control group); CA4P, Dox-loaded PEG-coated HAuNS (Dox@PEG-HAuNS), and ethiodized oil (CET group); or CA4P, Dox@PEG-HAuNS, ethiodized oil, and near-infrared irradiation (PTA-CET group). Temperature was recorded during laser irradiation. Findings were verified at postmortem histopathologic and/or autoradiographic examination. Wilcoxon rank-sum test and Pearson correlation analyses were performed. Results PEG-HAuNS uptake in CA4P-pretreated HCC tumors was significantly higher than that in non-CA4P-pretreated tumors at both 1 hour (P < .03) and 24 hours (P < .01). Mean ± standard deviation of tumor-to-liver PEG-HAuNS uptake ratios at 1 hour and 24 hours, respectively, were 5.63 ± 3.09 and 1.68 ± 0.77 in the CA4P-treated group and 1.29 ± 2.40 and 0.14 ± 0.11 in the non-CA4P-treated group. Micro-PET/CT allowed clear delineation of tumors, enabling quantitative imaging analysis. Laser irradiation increased temperature to 60°C and 43°C in the tumor and adjacent liver, respectively. Mean HCC tumor volumes 10 days after therapy were 1.68 cm3 ± 1.01, 3.96 cm3 ± 1.75, and 6.13 cm3 ± 2.27 in the PTA-CET, CET, and control groups, respectively, with significant differences between the PTA-CET group and other groups (P < .05). Conclusion CA4P pretreatment caused a higher concentration of Dox@PEG-HAuNS to be trapped inside the tumor, thereby enhancing the efficacy of anti-HCC treatment with PTA-CET in rats. © RSNA, 2016 Online supplemental material is available for this article.

Dataset Information

Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages.

Publications

Inducing cancer cell death by targeting its nucleus: solid gold nanospheres versus hollow gold nanocages.

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