R. Bai - Academia.edu (original) (raw)
Papers by R. Bai
ACS nano, Jan 20, 2015
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, ...
PLOS ONE, 2015
Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable... more Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO 2 NMs with different surface chemistryhydrophilic (NM-103) and hydrophobic (NM-104), two forms of and coated with triethoxycapryl silane (NM-111) and two SiO 2 NMs produced by two different manufacturing techniquesprecipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO 2 >TiO 2 ). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO 2 and SiO 2 , while the embryonic stem cell test (EST) classified the TiO 2 NMs as potentially 'weakembryotoxic' and ZnO and SiO 2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO 2 NM-203 > SiO 2 NM-200 > TiO 2 NM-104 > TiO 2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO 2 displayed higher toxicity compared with ZnO and SiO 2 . Importantly, the in vitro methodology applied could identify cell-and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects.
Nature communications, 2015
The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as... more The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82(OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82(OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82(OH)22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82(OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1α and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol i...
Toxicology Letters, 2014
Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing atten... more Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p<0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements was observed by synchrotron radiation X-ray fluorescence (SRXRF).…
Small, 2013
Multiwall carbon nanotubes (MWCNTs) have been widely used in many disciplines due to their unique... more Multiwall carbon nanotubes (MWCNTs) have been widely used in many disciplines due to their unique physical and chemical properties, but have also raised great concerns about their possible negative health impacts, especially through occupational exposure. Although recent studies have demonstrated that MWCNTs induce granuloma formation and/or fi brotic responses in the lungs of rats or mice, their cellular and molecular mechanisms remain largely unaddressed. Here, it is reported that the TGF-β /Smad signaling pathway can be activated by MWCNTs and play a critical role in MWCNT-induced pulmonary fi brosis. Firstly, in vivo data show that spontaneously hypertensive (SH) rats administered long MWCNTs (20-50 μ m) but not short MWCNTs (0.5-2 μ m) exhibit increased fi broblast proliferation, collagen deposition and granuloma formation in lung tissue. Secondly, the in vivo experiments also indicate that only long MWCNTs can signifi cantly activate macrophages and increase the production of transforming growth factor (TGF)-β 1, which induces the phosphorylation of Smad2 and then the expression of collagen I/III and extracellular matrix (ECM) protease inhibitors in lung tissues. Finally, the present in vitro studies further demonstrate that the TGF-β /Smad signaling pathway is indeed necessary for the expression of collagen III in fi broblast cells. Together, these data demonstrate that MWCNTs stimulate pulmonary fi brotic responses such as fi broblast proliferation and collagen deposition in a TGF-β /Smad-dependent manner. These observations also suggest that tube length acts as an important factor in MWCNT-induced macrophage activation and subsequent TGF-β 1 secretion. These in vivo and in vitro studies further highlight the potential adverse health effects that may occur following MWCNT exposure and provide a better understanding of the cellular and molecular mechanisms by which MWCNTs induce pulmonary fi brotic reactions.
Biomaterials, 2010
Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, l... more Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents.
PLoS ONE, 2008
Background: Signal regulate protein a (SIRPa) is involved in many functional aspects of monocytes... more Background: Signal regulate protein a (SIRPa) is involved in many functional aspects of monocytes. Here we investigate the role of SIRPa in regulating b 2 integrin-mediated monocyte adhesion, transendothelial migration (TEM) and phagocytosis.
Nanotoxicology, 2012
As a novel kind of nanomaterial with wide potential applications, the adverse effects of carbon n... more As a novel kind of nanomaterial with wide potential applications, the adverse effects of carbon nanotubes (CNTs) have recently received significant attention after respiratory exposure. In this study, single-wall carbon nanotubes (SWCNTs) containing different metal contents were intratracheally instilled into lungs of spontaneously hypertensive rats. Pulmonary and cardiovascular system alterations were evaluated at 24 and 72 h post-instillation. Biomarkers of inflammation, oxidative stress and cell damage in the bronchoalveolar lavage fluid (BALF) were increased significantly 24 h post-exposure of SWCNTs. The increased endothelin-1 levels in BALF and plasma and angiotensin I-converting enzyme in plasma suggested endothelial dysfunction in the pulmonary circulation and peripheral vascular thrombosis. These findings suggest that respiratory exposure to SWCNTs can induce acute pulmonary and cardiovascular responses and individuals with existing cardiovascular diseases are very susceptible to SWCNTs exposure. The co-existence of metal residues in SWCNTs can aggravate the adverse effects.
ACS nano, Jan 20, 2015
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, ...
PLOS ONE, 2015
Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable... more Nanomaterials (NMs) display many unique and useful physico-chemical properties. However, reliable approaches are needed for risk assessment of NMs. The present study was performed in the FP7-MARINA project, with the objective to identify and evaluate in vitro test methods for toxicity assessment in order to facilitate the development of an intelligent testing strategy (ITS). Six representative oxide NMs provided by the EC-JRC Nanomaterials Repository were tested in nine laboratories. The in vitro toxicity of NMs was evaluated in 12 cellular models representing 6 different target organs/systems (immune system, respiratory system, gastrointestinal system, reproductive organs, kidney and embryonic tissues). The toxicity assessment was conducted using 10 different assays for cytotoxicity, embryotoxicity, epithelial integrity, cytokine secretion and oxidative stress. Thorough physico-chemical characterization was performed for all tested NMs. Commercially relevant NMs with different physico-chemical properties were selected: two TiO 2 NMs with different surface chemistryhydrophilic (NM-103) and hydrophobic (NM-104), two forms of and coated with triethoxycapryl silane (NM-111) and two SiO 2 NMs produced by two different manufacturing techniquesprecipitated (NM-200) and pyrogenic (NM-203). Cell specific toxicity effects of all NMs were observed; macrophages were the most sensitive cell type after short-term exposures (24-72h) (ZnO>SiO 2 >TiO 2 ). Longer term exposure (7 to 21 days) significantly affected the cell barrier integrity in the presence of ZnO, but not TiO 2 and SiO 2 , while the embryonic stem cell test (EST) classified the TiO 2 NMs as potentially 'weakembryotoxic' and ZnO and SiO 2 NMs as 'non-embryotoxic'. A hazard ranking could be established for the representative NMs tested (ZnO NM-110 > ZnO NM-111 > SiO 2 NM-203 > SiO 2 NM-200 > TiO 2 NM-104 > TiO 2 NM-103). This ranking was different in the case of embryonic tissues, for which TiO 2 displayed higher toxicity compared with ZnO and SiO 2 . Importantly, the in vitro methodology applied could identify cell-and NM-specific responses, with a low variability observed between different test assays. Overall, this testing approach, based on a battery of cellular systems and test assays, complemented by an exhaustive physico-chemical characterization of NMs, could be deployed for the development of an ITS suitable for risk assessment of NMs. This study also provides a rich source of data for modeling of NM effects.
Nature communications, 2015
The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as... more The contemporary use of nanomedicines for cancer treatment has been largely limited to serving as carriers for existing therapeutic agents. Here, we provide definitive evidence that, the metallofullerenol nanomaterial Gd@C82(OH)22, while essentially not toxic to normal mammary epithelial cells, possesses intrinsic inhibitory activity against triple-negative breast cancer cells. Gd@C82(OH)22 blocks epithelial-to-mesenchymal transition with resultant efficient elimination of breast cancer stem cells (CSCs) resulting in abrogation of tumour initiation and metastasis. In normoxic conditions, Gd@C82(OH)22 mediates these effects by blocking TGF-β signalling. Moreover, under hypoxic conditions found in the tumour microenvironment, cellular uptake of Gd@C82(OH)22 is facilitated where it functions as a bi-potent inhibitor of HIF-1α and TGF-β activities, enhancing CSC elimination. These studies indicate that nanomaterials can be engineered to directly target CSCs. Thus, Gd-metallofullerenol i...
Toxicology Letters, 2014
Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing atten... more Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (p<0.05) but recovered slightly within exposure duration. Inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that CuNPs could enter the brain. Altered distribution of some important metal elements was observed by synchrotron radiation X-ray fluorescence (SRXRF).…
Small, 2013
Multiwall carbon nanotubes (MWCNTs) have been widely used in many disciplines due to their unique... more Multiwall carbon nanotubes (MWCNTs) have been widely used in many disciplines due to their unique physical and chemical properties, but have also raised great concerns about their possible negative health impacts, especially through occupational exposure. Although recent studies have demonstrated that MWCNTs induce granuloma formation and/or fi brotic responses in the lungs of rats or mice, their cellular and molecular mechanisms remain largely unaddressed. Here, it is reported that the TGF-β /Smad signaling pathway can be activated by MWCNTs and play a critical role in MWCNT-induced pulmonary fi brosis. Firstly, in vivo data show that spontaneously hypertensive (SH) rats administered long MWCNTs (20-50 μ m) but not short MWCNTs (0.5-2 μ m) exhibit increased fi broblast proliferation, collagen deposition and granuloma formation in lung tissue. Secondly, the in vivo experiments also indicate that only long MWCNTs can signifi cantly activate macrophages and increase the production of transforming growth factor (TGF)-β 1, which induces the phosphorylation of Smad2 and then the expression of collagen I/III and extracellular matrix (ECM) protease inhibitors in lung tissues. Finally, the present in vitro studies further demonstrate that the TGF-β /Smad signaling pathway is indeed necessary for the expression of collagen III in fi broblast cells. Together, these data demonstrate that MWCNTs stimulate pulmonary fi brotic responses such as fi broblast proliferation and collagen deposition in a TGF-β /Smad-dependent manner. These observations also suggest that tube length acts as an important factor in MWCNT-induced macrophage activation and subsequent TGF-β 1 secretion. These in vivo and in vitro studies further highlight the potential adverse health effects that may occur following MWCNT exposure and provide a better understanding of the cellular and molecular mechanisms by which MWCNTs induce pulmonary fi brotic reactions.
Biomaterials, 2010
Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, l... more Gold nanorods (Au NRs) have been recognized as promising materials for biomedical applications, like sensing, imaging, gene and drug delivery and therapy, but their toxicological issues are still controversial, especially for the Au NRs synthesized with seed-mediated method. In this study, we investigated the influence of aspect ratio and surface coating on their toxicity and cellular uptake. The cellular uptake is highly dependent on the aspect ratio and surface coating. However, the surface chemistry has the dominant roles since PDDAC-coated Au NRs exhibit a much greater ability to be internalized by the cells. The present data demonstrated shape-independent but coating-dependent cytotoxicity. Both the CTAB molecules left in the suspended solution and on the surface of Au NRs were identified as the actual cause of cytotoxicity. CTAB can enter cells with or without Au NRs, damage mitochondria, and then induce apoptosis. The effects of surface coating upon toxicity and cellular uptake were also examined using Au NRs with different coatings. When Au NRs were added into the medium, the proteins were quickly adsorbed onto the Au NRs that made the surface negatively charged. The surface charge may not directly affect the cellular uptake. We further demonstrated that the amount of serum proteins, especially for BSA, adsorbed on the Au NRs had a positive correlation with the capacity of Au NRs to enter cells. In addition, we have successfully revealed that the cationic PDDAC-coated Au NRs with an aspect ratio of 4 possess an ideal combination of both negligible toxicity and high cellular uptake efficiency, showing a great promise as photothermal therapeutic agents.
PLoS ONE, 2008
Background: Signal regulate protein a (SIRPa) is involved in many functional aspects of monocytes... more Background: Signal regulate protein a (SIRPa) is involved in many functional aspects of monocytes. Here we investigate the role of SIRPa in regulating b 2 integrin-mediated monocyte adhesion, transendothelial migration (TEM) and phagocytosis.
Nanotoxicology, 2012
As a novel kind of nanomaterial with wide potential applications, the adverse effects of carbon n... more As a novel kind of nanomaterial with wide potential applications, the adverse effects of carbon nanotubes (CNTs) have recently received significant attention after respiratory exposure. In this study, single-wall carbon nanotubes (SWCNTs) containing different metal contents were intratracheally instilled into lungs of spontaneously hypertensive rats. Pulmonary and cardiovascular system alterations were evaluated at 24 and 72 h post-instillation. Biomarkers of inflammation, oxidative stress and cell damage in the bronchoalveolar lavage fluid (BALF) were increased significantly 24 h post-exposure of SWCNTs. The increased endothelin-1 levels in BALF and plasma and angiotensin I-converting enzyme in plasma suggested endothelial dysfunction in the pulmonary circulation and peripheral vascular thrombosis. These findings suggest that respiratory exposure to SWCNTs can induce acute pulmonary and cardiovascular responses and individuals with existing cardiovascular diseases are very susceptible to SWCNTs exposure. The co-existence of metal residues in SWCNTs can aggravate the adverse effects.