The metabolic thermograms and heat output of mitochondria isolated from carp liver have been dete... more The metabolic thermograms and heat output of mitochondria isolated from carp liver have been determined by using an LKB bioactivity monitor. The thermogram can be divided into four parts: the lag phase, active recovery phase, stationary phase, and decline phase. The thermokinetic equation was established for the active recovery and decline phase of metabolism as follows: dP/dt =k mP (1-SP).
A nanoplatform of cancer-targeted nanocomposites is demonstrated by H. B. Chen and co-workers on ... more A nanoplatform of cancer-targeted nanocomposites is demonstrated by H. B. Chen and co-workers on page 3874 through the assembly of gadolinium oxide nanocrystals with a protein scaffold in conjugation with near-infrared cyanine dye, directed to trimodal near-infrared fluorescence/photoacoustics/magnetic-resonance imaging with complementary features, including ultrasensitivity, precise anatomical localization, and good spatial resolution, as well as smart photothermal efficacy with tumor ablation.
The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasi... more The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasis. Our previous study found that Gd@C82(OH)22 can suppress pancreatic cancer by inhibiting MMP-2/9 expression. In this study, we further explored the epigenetic mechanism of Gd@C82(OH)22 in human pancreatic cancer metastasis. Gd@C82(OH)22 suppressed tumor metastasis through down-regulation of metastasis-associated protein 1 (MTA1), HDAC1, HIF-1α, and MMP-2/9 and up-regulation of reversion-cysteine protein with the Kazal motif (RECK). The level of acetylation was increased in the promoter region of the RECK gene after Gd@C82(OH)22 treatment. The interaction of MTA1, HDAC1, and HIF-1α was inhibited by Gd@C82(OH)22. Furthermore, large-scale molecular dynamics simulations revealed Gd@C82(OH)22 could serve as an effective HDAC inhibitor to the protein-protein association between HDAC1 and MTA1, especially through MTA1's SANT and ELM2 dimerization domains. Our findings implicate Gd@C82(OH)...
Advanced materials (Deerfield Beach, Fla.), Jan 5, 2015
Core-shell upconversion nanoparticle@metal-organic framework (UCNP@MOF) nanostructures are constr... more Core-shell upconversion nanoparticle@metal-organic framework (UCNP@MOF) nanostructures are constructed by coating hexagonal NaYF4 :Yb,Er nanoparticle (NP) cores with amino-functionalized iron carboxylate MOF shells. These nanostructures combine the near-infrared optical property of UCNP cores and the T2 -magnetic response (MR) imaging property of MOF shells. After surface modification, the core-shell nanostructures are demonstrated as high-resolution nanoprobes for targeted luminescence/MR imaging both in vitro and in vivo.
To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to underst... more To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information of intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectrometry, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag0)n, to Ag+ ions and Ag-O-, then Ag-S- species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, ...
Advanced materials (Deerfield Beach, Fla.), Jan 21, 2015
Smart cyanine-grafted gadolinium oxide nanocrystals (Cy-GdNCs) obtained by albumin-based biominer... more Smart cyanine-grafted gadolinium oxide nanocrystals (Cy-GdNCs) obtained by albumin-based biomineralization are shown to be theranostic nanocomposites, with promising properties for trimodal near-infrared fluorescence/photoacoustics/magnetic resonance imaging-guided photothermal tumor ablation.
Recent advances in nanomedicine provide promising alternatives for cancer treatment that may impr... more Recent advances in nanomedicine provide promising alternatives for cancer treatment that may improve the survival of patients with metastatic disease. The goal of the present study was to evaluate graphene oxide (GO) as a potential anti-metastatic agent. For this purpose, GO was modified with polyethylene glycol (PEG) to form PEG-modified GO (PEG-GO), which improves its aqueous stability and biocompatibility. We show here that PEG-GO exhibited no apparent effects on the viability of breast cancer cells (MDA-MB-231, MDA-MB-436, and SK-BR-3) or non-cancerous cells (MCF-10A), but inhibited cancer cell migration in vitro and in vivo. Analysis of cellular energy metabolism revealed that PEG-GO significantly impaired mitochondrial oxidative phosphorylation (OXPHOS) in breast cancer cells; however, PEG-GO showed no effect on OXPHOS in non-cancerous cells. To explore the underlying mechanisms, a SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to qua...
The subcellular localization of Se and Hg and their cytosolic binding proteins, including cellula... more The subcellular localization of Se and Hg and their cytosolic binding proteins, including cellular oxidative status, in porcine liver and kidney have been studied by using samples from a chronic Hg-contaminated area and a non-Hg-contaminated area. Coaccumulation and redistribution of Se and Hg in subcellular fractions due to mercury exposure were found. The Hg and Se concentrations in tissues from Hg-exposed porcine were 80 fold and 5-20 fold higher than controls, respectively. Interestingly, the retention of both Se and Hg increased 10% in mitochondria, while decreased 10% in cytosol of Hg-exposed pig liver. Mercury was mainly in the form of MTs in the cytosol of the non-Hg-exposed porcine kidney. MT binds Hg in the cytosol with limited capacity, and the rest Hg was redistributed to the high molecular weight (MW) proteins (80-100 kDa) in the Hg-exposed group. The coaccumulation of Hg and Se was also found in high MW proteins, where their molar ratio tended to be 1:1. Moreover, the ...
Wei sheng yan jiu = Journal of hygiene research, 2004
To investigate the roles of essential trace element selenium and cellular antioxidative systems i... more To investigate the roles of essential trace element selenium and cellular antioxidative systems in human hepatocellular carcinoma, we analyzed cellular distribution of selenium and assayed cytosolic and mitochondrial superoxide dismutase, glutathione peroxidase, thioredoxin reductase, glutathione and total protein thiols in 10 control healthy subjects, 6 cases of hepatocellular carcinoma and 2 cases of normal liver adjacent to the hepatocellular carcinoma. In hepatoma tissues, the Se contents in lysosome (P < 0.05), microsome (P < 0.05) and cytosol were higher than in the control liver. In 2 cases, normal liver adjacent to hepatocellular carcinoma had decreased Se content. In hepatoma tissues, GSH and protein thiols content and activities of SOD, GSH-Px and TrxR were all much higher than in normal liver tissue. These findings suggested the antioxidative defense-related enzymes and antioxidant were largely regulated in hepatoma cells, whereas the cause is not clear and requires...
Electrical properties of cells determine most of the cellular functions, particularly ones which ... more Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (<2 V/cm) AC electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field....
The interactions between nanoparticles and macromolecules in the blood plasma dictate the biocomp... more The interactions between nanoparticles and macromolecules in the blood plasma dictate the biocompatibility and efficacy of nanotherapeutics. Accordingly, the properties of nanoparticles and endogenous biomolecules change at the nano-plasma interface. Here, we review the implications of such changes including toxicity, immunological recognition, molecular targeting, biodistribution, intracellular uptake, and drug release. Although this interface poses several challenges for nanomedicine, it also presents opportunities for exploiting nanoparticle-protein interactions.
Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the d... more Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the dominate reason for cancer-related mortality. In present work, DNA-wrapped gold nanorods with doxorubicin (DOX)-loading (GNR@DOX) were developed for treatment of metastatic breast cancer via a combination of chemotherapy and photothermal ablation. The GNR@DOX nanoparticles induced significant temperature elevation and DOX release upon irradiation with near infrared (NIR) light as shown in the test tube studies. It was found that GNR@DOX nanoparticles in combination with laser irradiation caused higher cytotoxicity than free DOX in 4T1 breast cancer cells. Animal experiment with an orthotropic 4T1 mammary tumor model demonstrated that GNR@DOX nanoplatform significantly reduced the growth of primary tumors and suppressed their lung metastasis. The Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) staining assays confirmed that the tumor growth inhibition and metastasis prevention o...
Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities of enzymes associ... more Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities of enzymes associated with the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice. Several physiologically relevant ROS were directly scavenged by nanoparticles, and lipid peroxidation was inhibited in this study. [Gd@C82(OH)22]n nanoparticles significantly reduced the electron spin resonance (ESR) signal of the stable 2,2-diphenyl-1-picryhydrazyl radical measured by ESR spectroscopy. Like-wise, studies using ESR with spin-trapping demonstrated efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet oxygen (1O2) by [Gd@C82(OH)22]n nanoparticles. In vitro studies using liposomes prepared from bovine liver phosphatidylcholine revealed that nanoparticles also had a strong inhibitory effect on lipid peroxidation. Consistent with their ability to scavenge ROS and inhibit lipid peroxidation, we determined that [Gd@C82(OH)22]n nanoparticles also protected cells subject...
The metabolic thermograms and heat output of mitochondria isolated from carp liver have been dete... more The metabolic thermograms and heat output of mitochondria isolated from carp liver have been determined by using an LKB bioactivity monitor. The thermogram can be divided into four parts: the lag phase, active recovery phase, stationary phase, and decline phase. The thermokinetic equation was established for the active recovery and decline phase of metabolism as follows: dP/dt =k mP (1-SP).
A nanoplatform of cancer-targeted nanocomposites is demonstrated by H. B. Chen and co-workers on ... more A nanoplatform of cancer-targeted nanocomposites is demonstrated by H. B. Chen and co-workers on page 3874 through the assembly of gadolinium oxide nanocrystals with a protein scaffold in conjugation with near-infrared cyanine dye, directed to trimodal near-infrared fluorescence/photoacoustics/magnetic-resonance imaging with complementary features, including ultrasensitivity, precise anatomical localization, and good spatial resolution, as well as smart photothermal efficacy with tumor ablation.
The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasi... more The treatment of pancreatic cancer frequently fails due to local recurrence and hepatic metastasis. Our previous study found that Gd@C82(OH)22 can suppress pancreatic cancer by inhibiting MMP-2/9 expression. In this study, we further explored the epigenetic mechanism of Gd@C82(OH)22 in human pancreatic cancer metastasis. Gd@C82(OH)22 suppressed tumor metastasis through down-regulation of metastasis-associated protein 1 (MTA1), HDAC1, HIF-1α, and MMP-2/9 and up-regulation of reversion-cysteine protein with the Kazal motif (RECK). The level of acetylation was increased in the promoter region of the RECK gene after Gd@C82(OH)22 treatment. The interaction of MTA1, HDAC1, and HIF-1α was inhibited by Gd@C82(OH)22. Furthermore, large-scale molecular dynamics simulations revealed Gd@C82(OH)22 could serve as an effective HDAC inhibitor to the protein-protein association between HDAC1 and MTA1, especially through MTA1's SANT and ELM2 dimerization domains. Our findings implicate Gd@C82(OH)...
Advanced materials (Deerfield Beach, Fla.), Jan 5, 2015
Core-shell upconversion nanoparticle@metal-organic framework (UCNP@MOF) nanostructures are constr... more Core-shell upconversion nanoparticle@metal-organic framework (UCNP@MOF) nanostructures are constructed by coating hexagonal NaYF4 :Yb,Er nanoparticle (NP) cores with amino-functionalized iron carboxylate MOF shells. These nanostructures combine the near-infrared optical property of UCNP cores and the T2 -magnetic response (MR) imaging property of MOF shells. After surface modification, the core-shell nanostructures are demonstrated as high-resolution nanoprobes for targeted luminescence/MR imaging both in vitro and in vivo.
To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to underst... more To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information of intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectrometry, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag0)n, to Ag+ ions and Ag-O-, then Ag-S- species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, ...
Advanced materials (Deerfield Beach, Fla.), Jan 21, 2015
Smart cyanine-grafted gadolinium oxide nanocrystals (Cy-GdNCs) obtained by albumin-based biominer... more Smart cyanine-grafted gadolinium oxide nanocrystals (Cy-GdNCs) obtained by albumin-based biomineralization are shown to be theranostic nanocomposites, with promising properties for trimodal near-infrared fluorescence/photoacoustics/magnetic resonance imaging-guided photothermal tumor ablation.
Recent advances in nanomedicine provide promising alternatives for cancer treatment that may impr... more Recent advances in nanomedicine provide promising alternatives for cancer treatment that may improve the survival of patients with metastatic disease. The goal of the present study was to evaluate graphene oxide (GO) as a potential anti-metastatic agent. For this purpose, GO was modified with polyethylene glycol (PEG) to form PEG-modified GO (PEG-GO), which improves its aqueous stability and biocompatibility. We show here that PEG-GO exhibited no apparent effects on the viability of breast cancer cells (MDA-MB-231, MDA-MB-436, and SK-BR-3) or non-cancerous cells (MCF-10A), but inhibited cancer cell migration in vitro and in vivo. Analysis of cellular energy metabolism revealed that PEG-GO significantly impaired mitochondrial oxidative phosphorylation (OXPHOS) in breast cancer cells; however, PEG-GO showed no effect on OXPHOS in non-cancerous cells. To explore the underlying mechanisms, a SILAC (Stable Isotope Labeling by Amino acids in Cell culture) labeling strategy was used to qua...
The subcellular localization of Se and Hg and their cytosolic binding proteins, including cellula... more The subcellular localization of Se and Hg and their cytosolic binding proteins, including cellular oxidative status, in porcine liver and kidney have been studied by using samples from a chronic Hg-contaminated area and a non-Hg-contaminated area. Coaccumulation and redistribution of Se and Hg in subcellular fractions due to mercury exposure were found. The Hg and Se concentrations in tissues from Hg-exposed porcine were 80 fold and 5-20 fold higher than controls, respectively. Interestingly, the retention of both Se and Hg increased 10% in mitochondria, while decreased 10% in cytosol of Hg-exposed pig liver. Mercury was mainly in the form of MTs in the cytosol of the non-Hg-exposed porcine kidney. MT binds Hg in the cytosol with limited capacity, and the rest Hg was redistributed to the high molecular weight (MW) proteins (80-100 kDa) in the Hg-exposed group. The coaccumulation of Hg and Se was also found in high MW proteins, where their molar ratio tended to be 1:1. Moreover, the ...
Wei sheng yan jiu = Journal of hygiene research, 2004
To investigate the roles of essential trace element selenium and cellular antioxidative systems i... more To investigate the roles of essential trace element selenium and cellular antioxidative systems in human hepatocellular carcinoma, we analyzed cellular distribution of selenium and assayed cytosolic and mitochondrial superoxide dismutase, glutathione peroxidase, thioredoxin reductase, glutathione and total protein thiols in 10 control healthy subjects, 6 cases of hepatocellular carcinoma and 2 cases of normal liver adjacent to the hepatocellular carcinoma. In hepatoma tissues, the Se contents in lysosome (P < 0.05), microsome (P < 0.05) and cytosol were higher than in the control liver. In 2 cases, normal liver adjacent to hepatocellular carcinoma had decreased Se content. In hepatoma tissues, GSH and protein thiols content and activities of SOD, GSH-Px and TrxR were all much higher than in normal liver tissue. These findings suggested the antioxidative defense-related enzymes and antioxidant were largely regulated in hepatoma cells, whereas the cause is not clear and requires...
Electrical properties of cells determine most of the cellular functions, particularly ones which ... more Electrical properties of cells determine most of the cellular functions, particularly ones which occur in the cell's membrane. Manipulation of these electrical properties may provide a powerful electrotherapy option for the treatment of cancer as cancerous cells have been shown to be more electronegative than normal proliferating cells. Previously, we used an electrical impedance sensing system (EIS) to explore the responses of cancerous SKOV3 cells and normal HUVEC cells to low intensity (<2 V/cm) AC electric fields, determining that the optimal frequency for SKOV3 proliferation arrest was 200 kHz, without harming the non-cancerous HUVECs. In this study, to determine if these effects are cell type dependant, human breast adenocarcinoma cells (MCF7) were subjected to a range of frequencies (50 kHz-2 MHz) similar to the previously tested SKOV3. For the MCF7, an optimal frequency of 100 kHz was determined using the EIS, indicating a higher sensitivity towards the applied field....
The interactions between nanoparticles and macromolecules in the blood plasma dictate the biocomp... more The interactions between nanoparticles and macromolecules in the blood plasma dictate the biocompatibility and efficacy of nanotherapeutics. Accordingly, the properties of nanoparticles and endogenous biomolecules change at the nano-plasma interface. Here, we review the implications of such changes including toxicity, immunological recognition, molecular targeting, biodistribution, intracellular uptake, and drug release. Although this interface poses several challenges for nanomedicine, it also presents opportunities for exploiting nanoparticle-protein interactions.
Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the d... more Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the dominate reason for cancer-related mortality. In present work, DNA-wrapped gold nanorods with doxorubicin (DOX)-loading (GNR@DOX) were developed for treatment of metastatic breast cancer via a combination of chemotherapy and photothermal ablation. The GNR@DOX nanoparticles induced significant temperature elevation and DOX release upon irradiation with near infrared (NIR) light as shown in the test tube studies. It was found that GNR@DOX nanoparticles in combination with laser irradiation caused higher cytotoxicity than free DOX in 4T1 breast cancer cells. Animal experiment with an orthotropic 4T1 mammary tumor model demonstrated that GNR@DOX nanoplatform significantly reduced the growth of primary tumors and suppressed their lung metastasis. The Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) staining assays confirmed that the tumor growth inhibition and metastasis prevention o...
Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities of enzymes associ... more Intraperitoneal injection of [Gd@C82(OH)22]n nanoparticles decreased activities of enzymes associated with the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice. Several physiologically relevant ROS were directly scavenged by nanoparticles, and lipid peroxidation was inhibited in this study. [Gd@C82(OH)22]n nanoparticles significantly reduced the electron spin resonance (ESR) signal of the stable 2,2-diphenyl-1-picryhydrazyl radical measured by ESR spectroscopy. Like-wise, studies using ESR with spin-trapping demonstrated efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet oxygen (1O2) by [Gd@C82(OH)22]n nanoparticles. In vitro studies using liposomes prepared from bovine liver phosphatidylcholine revealed that nanoparticles also had a strong inhibitory effect on lipid peroxidation. Consistent with their ability to scavenge ROS and inhibit lipid peroxidation, we determined that [Gd@C82(OH)22]n nanoparticles also protected cells subject...
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Papers by Chunying Chen