Single-walled carbon nanotubes (SWCNTs) implementation in a variety of biomedical applications fr... more Single-walled carbon nanotubes (SWCNTs) implementation in a variety of biomedical applications from bioimaging, to controlled drug delivery and cellular-directed alignment for muscle myofiber fabrication, has raised awareness of their potential toxicity. Nanotubes structural aspects which resemble asbestos, as well as their ability to induce cyto and genotoxicity upon interaction with biological systems by generating reactive oxygen species or inducing membrane damage, just to name a few, have led to focused efforts aimed to assess associated risks prior their user implementation. In this study, we employed a non-invasive and real-time electric cell impedance sensing (ECIS) platform to monitor behavior of lung epithelial cells upon exposure to a library of SWCNTs with user-defined physicochemical properties. Using the natural sensitivity of the cells, we evaluated SWCNT-induced cellular changes in relation to cell attachment, cell-cell interactions and cell viability respectively. Our methods have the potential to lead to the development of standardized assays for risk assessment of other nanomaterials as well as risk differentiation based on the nanomaterials surface chemistry, purity and agglomeration state.
The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial p... more The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial properties and the exposure duration. Herein we used a multi-tier strategy to investigate the relationship between user-characterized multi-walled carbon nanotubes (MWCNTs) exposure duration and their induced biochemical and biomechanical effects on model human lung epithelial cells (BEAS-2B). Our results showed that exposure to MWCNTs leads to time-dependent intracellular uptake and generation of reactive oxygen species (ROS), along with time-dependent gradual changes in cellular biomechanical properties. In particular, the amount of internalized MWCNTs followed a sigmoidal curve with the majority of the MWCNTs being internalized within 6h of exposure; further, the sigmoidal uptake correlated with the changes in the oxidative levels and cellular biomechanical properties respectively. Our study provides new insights into the time-dependent induced toxicity caused by exposure to occupationally relevant doses of MWCNTs and could potentially help establish bases for early risk assessments of other nanomaterials toxicological profiles.
Abstract Carbon nanotubes (CNTs) are promising to be the next generation of viable tools for bioa... more Abstract Carbon nanotubes (CNTs) are promising to be the next generation of viable tools for bioapplications. Further advances in such bioapplications may depend on improved understanding of CNTs physical and chemical properties as well as control over their biocompatibility. Herein we performed a systematic study to show how acid oxidation treatment changes CNTs physical and chemical properties and leads to improved CNTs biocompatibility. Specifically, by incubating CNTs in a strong acid mixture we created a user-defined library of CNTs samples with different characteristics as recorded using Raman energy dispersive X-ray spectroscopy, atomic force microscopy, or solubility tests. Systematically characterized CNTs were subsequently tested for their biocompatibility in relation to human epithelial cells or enzymes. Such selected examples are building pertinent relationships between CNTs biocompatibility and their intrinsic properties by showing that acid oxidation treatment lowers CNTs toxicity providing feasible platforms to be used for biomedical applications or the next generation of biosensors.
Toxicity of engineered nanomaterials is associated with their inherent properties, both physical ... more Toxicity of engineered nanomaterials is associated with their inherent properties, both physical and chemical. Recent studies have shown that exposure to multi-walled carbon nanotubes (MWCNTs) promotes tumors and tumor-associated pathologies and lead to carcinogenesis in model in vivo systems. Here in we examined the potential of purified MWCNTs used at occupationally relevant exposure doses for particles not otherwise regulated to affect human lung epithelial cells. The uptake of the purified MWCNTs was evaluated using fluorescence activated cell sorting (FACS), while the effects on cell fate were assessed using 2-(4-iodophenyl)-3-(4nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium salt colorimetric assay, cell cycle and
Combinatorial Real-Time High Throughput Analyses of Cell Behavior Upon Exposure to Analytes By Re... more Combinatorial Real-Time High Throughput Analyses of Cell Behavior Upon Exposure to Analytes By Reem Eldawud The majority of current techniques to assess the toxicity of analytes (i.e., nanomaterials, drugs and toxins) in vitro rely on the application of affinity or catalytic recognition elements (i.e., biosensors), their activity, sensitivity and selectivity, as well as the processing power of micro-and opto-detection devices. For instance, water-soluble tetrazolium (WST-1) assay is among the most common techniques used to measure the viability of cells following exposure. Specifically, in this assay a catalytic biosensor (tetrazolium salt) is reduced by cellular NAD(P)H-dependent oxidoreductase or mitochondrial dehydrogenases resulting in colorimetric changes quantified using a UV-Vis spectrophotometer (detection element). Similarly, imaging of cellular components mainly relies on the application of affinity biosensors that bind to selected cellular organelles or proteins and subsequently emit a fluorescent signal upon detection using fluorescence microscopy. Although, the majority of these assays and techniques have high sensitivity, stability and reliability, inaccurate measurements and false positives may occur especially when detecting the toxicity of nanoparticles, such as carbon nanotubes (CNTs). In principle, the high surface area of
Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is i... more Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is incorporated into polymers to form nanocomposites with enhanced mechanical strength, barrier and flammability properties used for food packaging, automotive, and medical devices. However, with implementation in such consumer applications, the interaction of montmorillonite-based composites or derived byproducts with biological systems needs to be investigated. Herein we examined the potential of Cloisite Na(+) (pristine) and Cloisite 30B (organically modified montmorillonite nanoclay) and their thermally degraded byproducts' to induce toxicity in model human lung epithelial cells. The experimental set-up mimicked biological exposure in manufacturing and disposal areas and employed cellular treatments with occupationally relevant doses of nanoclays previously characterized using spectroscopical and microscopical approaches. For nanoclay-cellular interactions and for cellular analyses r...
Heterogenous photocatalysis is widely used for waste-water treatment and degradation of pollutant... more Heterogenous photocatalysis is widely used for waste-water treatment and degradation of pollutants and promises to advance the science of alternative materials with visible photo-excitations abilities. However, there are still fundamental material properties and processes that need to be understood in order to increase user-tailored catalytic systems' performance and efficiency, while ensuring their optimized reactivities and large-scale development and implementation. Herein we developed graphene-based hybrid composites to be used as efficient nanocatalysts with increased ability to absorb visible light, that retain high corrosionresistance properties when used in solution, and provide energy levels that match their reduction and oxidation half-reactions. Using both photo-deposition and photoreduction methods, we first created platinum/tungsten trioxide conjugates with physico-chemical characteristics investigated by microscopical and spectroscopical analyses, and further decorated such conjugates onto graphene surfaces to create the hybrids. Our results demonstrate that the synthesized hybrids can degrade a model azo dye and further, show that graphene plays an important role in delaying electron transfer at its interface, with such effect being exploited for possible integration in the next generation of clean energy systems.
Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for ... more Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo setups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarsegrained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.
ABSTRACT Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications,... more ABSTRACT Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their implementation is currently being hindered by many uncertainties regarding their toxicity and fate inside the biological systems. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation and metal impurities, just to name a few. However, due to the various types of CNTs being synthesized every day along with the different surface functionalization techniques, there is no fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs with different physico-chemical properties. In this research, we provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs using a combination of electronic and cell-based techniques. Our analyses rely on a non-invasive electronic cell impedance sensing (ECIS) platform to provide real-time measurements of cell adhesion, cell-cell interactions as well as changes in cellular morphology upon exposure to CNTs with user-defined physical and chemical properties. The approach is complemented by standard microscopy techniques as well as conventional in vitro cellular-based assays, such as cell cycle analysis, cell proliferation and viability, in order to derive structure-function relations associated with the cytotoxic and apoptotic events induced by exposure to CNTs. Our results correlated the different physico-chemical properties of CNTs with the various biological responses and provided mechanistic insights into their Cyto- and genotoxic effects. Out study help define a novel platform for nanomaterials toxicity analysis and thus could expand the biomedical applications of CNTs and other nanomaterials.
Carbon nanotubes (CNTs) exhibit unique properties that make them attractive candidates for the de... more Carbon nanotubes (CNTs) exhibit unique properties that make them attractive candidates for the delivery of therapeutic molecules, genes and drugs. However, advances in the biomedical applications of CNTs are being hindered by uncertainties associated with their cellular uptake and delivery mechanisms as well as their fate inside the biological systems. Recent reports have shown that CNTs toxicity can be attributed to metal impurities, length, size, coating, uptake, or internalization. However, there are no reports that provide fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs. In this research, a new approach is used to assess the toxicity of a wide library of surface modified CNTs incubated with human lung epithelial cells (BEAS-2B) in real time. This non-invasive technique relies on an electrical cell impedance sensing system (ECIS) used as a proxy to measure morphological changes and cellular interactions upon exposure...
The clinical applications of digitoxin as a cardiac glycoside have been halted by many concerns a... more The clinical applications of digitoxin as a cardiac glycoside have been halted by many concerns associated with its cardiac toxicity. Recently it was shown that the toxic profiles induced by therapeutic ranges of digitoxin exposure are selective to many types of neoplastic cells from breast to prostate and lung cancer, making this drug an attractive candidate for chemotherapies. The anticancer potency of digitoxin lays in its trisaccharide moiety linked to a steroid core. Further research has shown that synthetic manipulation of digitoxin structure leads to more potent analogues. In this research, a new approach is used to characterize and quantify the cellular behavior of immortalized and tumorigenic human lung cells (BEAS-2B and H460 respectively) upon exposure to different concentrations of digitoxin and synthetic monosaccharide analogue (D6-MA) in real time. The approach relies on an electrical cell impedance sensing system (ECIS) used as a proxy to measure the morphological cha...
Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their im... more Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their implementation is currently being hindered by many uncertainties regarding their toxicity and fate inside the biological systems. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation and metal impurities, just to name a few. However, due to the various types of CNTs being synthesized every day along with the different surface functionalization techniques, there is no fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs with different physico-chemical properties. In this research, we provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs using a combination of electronic and cell-based techniques. Our analyses rely on a non-invasive electronic cell impedance sensing (ECIS) platform to provide real-time measurements of cell adhesio...
Digitoxin is a naturally occurring cardiac glycoside, well known for its efficiency in the treatm... more Digitoxin is a naturally occurring cardiac glycoside, well known for its efficiency in the treatment of congestive heart failure and arrhythmias. Recently, several reports have shown that digitoxin exhibits anti-neoplastic effects against several types of cancer ranging from breast to colon cancer, and from leukemia to lung cancer, suggesting digitoxin’s potential as a chemotherapeutic agent. The anticancer potency of digitoxin lies in its trisaccharide moiety which could be synthetically manipulated to produce a library of analogues. In our research we used an electrical cell impedance sensing system (ECIS) as a proxy to assess the cellular behavior of immortalized and tumorigenic human lung cells (BEAS-2B and H460 respectively) upon exposure to digitoxin and a synthetic monosaccharide (D6-MA). Our highthroughput, non-invasive approach employed arrays with gold electrodes as immobilization platforms to measure the changes in cellular attachment, migration and cell-cell interactions...
The unique intrinsic properties of carbon nanotubes (CNTs) make them potential candidates for a w... more The unique intrinsic properties of carbon nanotubes (CNTs) make them potential candidates for a wide range of biomedical applications spanning bio-imaging, disease targeting, and delivery of genes and drugs. Therefore, in-depth analysis of their toxicity and fate inside biological systems is crucial prior to their application. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation or metal impurities to name a few. However, due to the various types of CNTs and the different surface functionalizing techniques, there are many discrepancies in literature and limited understanding of their toxicological and pharmacological profiles. In this research, we employed an electric cell impedance sensing device to provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs with different physical and chemical properties. This non-invasive approach employs arrays with gold electrodes as immobilizatio...
Carbon nanotubes (CNTs) are applied for a variety of applications from nanocircuits, to hydrogen ... more Carbon nanotubes (CNTs) are applied for a variety of applications from nanocircuits, to hydrogen storage devices, and from opticals fibers to conductive plastics. Recently, their functionalization with biomolecules offer opportunities for exciting biological and biomedical applications in drug delivery or bioimaging. However, because of their interactions with biological systems and their ability to translocate and persist into the circulatory and lymphatic systems and tissues, concerns about CNTs intrinsic toxicity have risen. It is thus necessary to develop significant and sensitive advances analysis technologies for real time investigation of CNTs toxicity. Our research aims at elucidating the mechanisms involved in CNTs internalization and association with cellular systems by evaluating the overall effects on of CNTs on cellular biophysical properties-biomechanics. To unravel the biomolecular mechanisms of such interactions, we used Fluorescence Activated Cell Sorting (FACS) and...
The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial p... more The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial properties and the exposure duration.
Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their im... more Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their implementation is currently being hindered by many uncertainties regarding their toxicity and fate inside the biological systems. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation and metal impurities, just to name a few. However, due to the various types of CNTs being synthesized every day along with the different surface functionalization techniques, there is no fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs with different physico-chemical properties. In this research, we provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs using a combination of electronic and cell-based techniques. Our analyses rely on a non-invasive electronic cell impedance sensing (ECIS) platform to provide real-time measurements of cell adhesio...
Single-walled carbon nanotubes (SWCNTs) implementation in a variety of biomedical applications fr... more Single-walled carbon nanotubes (SWCNTs) implementation in a variety of biomedical applications from bioimaging, to controlled drug delivery and cellular-directed alignment for muscle myofiber fabrication, has raised awareness of their potential toxicity. Nanotubes structural aspects which resemble asbestos, as well as their ability to induce cyto and genotoxicity upon interaction with biological systems by generating reactive oxygen species or inducing membrane damage, just to name a few, have led to focused efforts aimed to assess associated risks prior their user implementation. In this study, we employed a non-invasive and real-time electric cell impedance sensing (ECIS) platform to monitor behavior of lung epithelial cells upon exposure to a library of SWCNTs with user-defined physicochemical properties. Using the natural sensitivity of the cells, we evaluated SWCNT-induced cellular changes in relation to cell attachment, cell-cell interactions and cell viability respectively. Our methods have the potential to lead to the development of standardized assays for risk assessment of other nanomaterials as well as risk differentiation based on the nanomaterials surface chemistry, purity and agglomeration state.
The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial p... more The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial properties and the exposure duration. Herein we used a multi-tier strategy to investigate the relationship between user-characterized multi-walled carbon nanotubes (MWCNTs) exposure duration and their induced biochemical and biomechanical effects on model human lung epithelial cells (BEAS-2B). Our results showed that exposure to MWCNTs leads to time-dependent intracellular uptake and generation of reactive oxygen species (ROS), along with time-dependent gradual changes in cellular biomechanical properties. In particular, the amount of internalized MWCNTs followed a sigmoidal curve with the majority of the MWCNTs being internalized within 6h of exposure; further, the sigmoidal uptake correlated with the changes in the oxidative levels and cellular biomechanical properties respectively. Our study provides new insights into the time-dependent induced toxicity caused by exposure to occupationally relevant doses of MWCNTs and could potentially help establish bases for early risk assessments of other nanomaterials toxicological profiles.
Abstract Carbon nanotubes (CNTs) are promising to be the next generation of viable tools for bioa... more Abstract Carbon nanotubes (CNTs) are promising to be the next generation of viable tools for bioapplications. Further advances in such bioapplications may depend on improved understanding of CNTs physical and chemical properties as well as control over their biocompatibility. Herein we performed a systematic study to show how acid oxidation treatment changes CNTs physical and chemical properties and leads to improved CNTs biocompatibility. Specifically, by incubating CNTs in a strong acid mixture we created a user-defined library of CNTs samples with different characteristics as recorded using Raman energy dispersive X-ray spectroscopy, atomic force microscopy, or solubility tests. Systematically characterized CNTs were subsequently tested for their biocompatibility in relation to human epithelial cells or enzymes. Such selected examples are building pertinent relationships between CNTs biocompatibility and their intrinsic properties by showing that acid oxidation treatment lowers CNTs toxicity providing feasible platforms to be used for biomedical applications or the next generation of biosensors.
Toxicity of engineered nanomaterials is associated with their inherent properties, both physical ... more Toxicity of engineered nanomaterials is associated with their inherent properties, both physical and chemical. Recent studies have shown that exposure to multi-walled carbon nanotubes (MWCNTs) promotes tumors and tumor-associated pathologies and lead to carcinogenesis in model in vivo systems. Here in we examined the potential of purified MWCNTs used at occupationally relevant exposure doses for particles not otherwise regulated to affect human lung epithelial cells. The uptake of the purified MWCNTs was evaluated using fluorescence activated cell sorting (FACS), while the effects on cell fate were assessed using 2-(4-iodophenyl)-3-(4nitrophenyl)-5-(2, 4-disulfophenyl)-2H-tetrazolium salt colorimetric assay, cell cycle and
Combinatorial Real-Time High Throughput Analyses of Cell Behavior Upon Exposure to Analytes By Re... more Combinatorial Real-Time High Throughput Analyses of Cell Behavior Upon Exposure to Analytes By Reem Eldawud The majority of current techniques to assess the toxicity of analytes (i.e., nanomaterials, drugs and toxins) in vitro rely on the application of affinity or catalytic recognition elements (i.e., biosensors), their activity, sensitivity and selectivity, as well as the processing power of micro-and opto-detection devices. For instance, water-soluble tetrazolium (WST-1) assay is among the most common techniques used to measure the viability of cells following exposure. Specifically, in this assay a catalytic biosensor (tetrazolium salt) is reduced by cellular NAD(P)H-dependent oxidoreductase or mitochondrial dehydrogenases resulting in colorimetric changes quantified using a UV-Vis spectrophotometer (detection element). Similarly, imaging of cellular components mainly relies on the application of affinity biosensors that bind to selected cellular organelles or proteins and subsequently emit a fluorescent signal upon detection using fluorescence microscopy. Although, the majority of these assays and techniques have high sensitivity, stability and reliability, inaccurate measurements and false positives may occur especially when detecting the toxicity of nanoparticles, such as carbon nanotubes (CNTs). In principle, the high surface area of
Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is i... more Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is incorporated into polymers to form nanocomposites with enhanced mechanical strength, barrier and flammability properties used for food packaging, automotive, and medical devices. However, with implementation in such consumer applications, the interaction of montmorillonite-based composites or derived byproducts with biological systems needs to be investigated. Herein we examined the potential of Cloisite Na(+) (pristine) and Cloisite 30B (organically modified montmorillonite nanoclay) and their thermally degraded byproducts' to induce toxicity in model human lung epithelial cells. The experimental set-up mimicked biological exposure in manufacturing and disposal areas and employed cellular treatments with occupationally relevant doses of nanoclays previously characterized using spectroscopical and microscopical approaches. For nanoclay-cellular interactions and for cellular analyses r...
Heterogenous photocatalysis is widely used for waste-water treatment and degradation of pollutant... more Heterogenous photocatalysis is widely used for waste-water treatment and degradation of pollutants and promises to advance the science of alternative materials with visible photo-excitations abilities. However, there are still fundamental material properties and processes that need to be understood in order to increase user-tailored catalytic systems' performance and efficiency, while ensuring their optimized reactivities and large-scale development and implementation. Herein we developed graphene-based hybrid composites to be used as efficient nanocatalysts with increased ability to absorb visible light, that retain high corrosionresistance properties when used in solution, and provide energy levels that match their reduction and oxidation half-reactions. Using both photo-deposition and photoreduction methods, we first created platinum/tungsten trioxide conjugates with physico-chemical characteristics investigated by microscopical and spectroscopical analyses, and further decorated such conjugates onto graphene surfaces to create the hybrids. Our results demonstrate that the synthesized hybrids can degrade a model azo dye and further, show that graphene plays an important role in delaying electron transfer at its interface, with such effect being exploited for possible integration in the next generation of clean energy systems.
Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for ... more Nanodiamonds (NDs) are an emerging class of engineered nanomaterials that hold great promise for the next generation of bionanotechnological products to be used for drug and gene delivery, or for bio-imaging and biosensing. Previous studies have shown that upon their cellular uptake, NDs exhibit high biocompatibility in various in vitro and in vivo setups. Herein we hypothesized that the increased NDs biocompatibility is a result of minimum membrane perturbations and their reduced ability to induce disruption or damage during cellular translocation. Using multi-scale combinatorial approaches that simulate ND-membrane interactions, we correlated NDs real-time cellular uptake and kinetics with the ND-induced membrane fluctuations to derive energy requirements for the uptake to occur. Our discrete and real-time analyses showed that the majority of NDs internalization occurs within 2 h of cellular exposure, however, with no effects on cellular viability, proliferation or cellular behavior. Furthermore, our simulation analyses using coarsegrained models identified key changes in the energy profile, membrane deformation and recovery time, all functions of the average ND or ND-based agglomerate size. Understanding the mechanisms responsible for ND-cell membrane interactions could possibly advance their implementation in various biomedical applications.
ABSTRACT Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications,... more ABSTRACT Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their implementation is currently being hindered by many uncertainties regarding their toxicity and fate inside the biological systems. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation and metal impurities, just to name a few. However, due to the various types of CNTs being synthesized every day along with the different surface functionalization techniques, there is no fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs with different physico-chemical properties. In this research, we provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs using a combination of electronic and cell-based techniques. Our analyses rely on a non-invasive electronic cell impedance sensing (ECIS) platform to provide real-time measurements of cell adhesion, cell-cell interactions as well as changes in cellular morphology upon exposure to CNTs with user-defined physical and chemical properties. The approach is complemented by standard microscopy techniques as well as conventional in vitro cellular-based assays, such as cell cycle analysis, cell proliferation and viability, in order to derive structure-function relations associated with the cytotoxic and apoptotic events induced by exposure to CNTs. Our results correlated the different physico-chemical properties of CNTs with the various biological responses and provided mechanistic insights into their Cyto- and genotoxic effects. Out study help define a novel platform for nanomaterials toxicity analysis and thus could expand the biomedical applications of CNTs and other nanomaterials.
Carbon nanotubes (CNTs) exhibit unique properties that make them attractive candidates for the de... more Carbon nanotubes (CNTs) exhibit unique properties that make them attractive candidates for the delivery of therapeutic molecules, genes and drugs. However, advances in the biomedical applications of CNTs are being hindered by uncertainties associated with their cellular uptake and delivery mechanisms as well as their fate inside the biological systems. Recent reports have shown that CNTs toxicity can be attributed to metal impurities, length, size, coating, uptake, or internalization. However, there are no reports that provide fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs. In this research, a new approach is used to assess the toxicity of a wide library of surface modified CNTs incubated with human lung epithelial cells (BEAS-2B) in real time. This non-invasive technique relies on an electrical cell impedance sensing system (ECIS) used as a proxy to measure morphological changes and cellular interactions upon exposure...
The clinical applications of digitoxin as a cardiac glycoside have been halted by many concerns a... more The clinical applications of digitoxin as a cardiac glycoside have been halted by many concerns associated with its cardiac toxicity. Recently it was shown that the toxic profiles induced by therapeutic ranges of digitoxin exposure are selective to many types of neoplastic cells from breast to prostate and lung cancer, making this drug an attractive candidate for chemotherapies. The anticancer potency of digitoxin lays in its trisaccharide moiety linked to a steroid core. Further research has shown that synthetic manipulation of digitoxin structure leads to more potent analogues. In this research, a new approach is used to characterize and quantify the cellular behavior of immortalized and tumorigenic human lung cells (BEAS-2B and H460 respectively) upon exposure to different concentrations of digitoxin and synthetic monosaccharide analogue (D6-MA) in real time. The approach relies on an electrical cell impedance sensing system (ECIS) used as a proxy to measure the morphological cha...
Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their im... more Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their implementation is currently being hindered by many uncertainties regarding their toxicity and fate inside the biological systems. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation and metal impurities, just to name a few. However, due to the various types of CNTs being synthesized every day along with the different surface functionalization techniques, there is no fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs with different physico-chemical properties. In this research, we provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs using a combination of electronic and cell-based techniques. Our analyses rely on a non-invasive electronic cell impedance sensing (ECIS) platform to provide real-time measurements of cell adhesio...
Digitoxin is a naturally occurring cardiac glycoside, well known for its efficiency in the treatm... more Digitoxin is a naturally occurring cardiac glycoside, well known for its efficiency in the treatment of congestive heart failure and arrhythmias. Recently, several reports have shown that digitoxin exhibits anti-neoplastic effects against several types of cancer ranging from breast to colon cancer, and from leukemia to lung cancer, suggesting digitoxin’s potential as a chemotherapeutic agent. The anticancer potency of digitoxin lies in its trisaccharide moiety which could be synthetically manipulated to produce a library of analogues. In our research we used an electrical cell impedance sensing system (ECIS) as a proxy to assess the cellular behavior of immortalized and tumorigenic human lung cells (BEAS-2B and H460 respectively) upon exposure to digitoxin and a synthetic monosaccharide (D6-MA). Our highthroughput, non-invasive approach employed arrays with gold electrodes as immobilization platforms to measure the changes in cellular attachment, migration and cell-cell interactions...
The unique intrinsic properties of carbon nanotubes (CNTs) make them potential candidates for a w... more The unique intrinsic properties of carbon nanotubes (CNTs) make them potential candidates for a wide range of biomedical applications spanning bio-imaging, disease targeting, and delivery of genes and drugs. Therefore, in-depth analysis of their toxicity and fate inside biological systems is crucial prior to their application. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation or metal impurities to name a few. However, due to the various types of CNTs and the different surface functionalizing techniques, there are many discrepancies in literature and limited understanding of their toxicological and pharmacological profiles. In this research, we employed an electric cell impedance sensing device to provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs with different physical and chemical properties. This non-invasive approach employs arrays with gold electrodes as immobilizatio...
Carbon nanotubes (CNTs) are applied for a variety of applications from nanocircuits, to hydrogen ... more Carbon nanotubes (CNTs) are applied for a variety of applications from nanocircuits, to hydrogen storage devices, and from opticals fibers to conductive plastics. Recently, their functionalization with biomolecules offer opportunities for exciting biological and biomedical applications in drug delivery or bioimaging. However, because of their interactions with biological systems and their ability to translocate and persist into the circulatory and lymphatic systems and tissues, concerns about CNTs intrinsic toxicity have risen. It is thus necessary to develop significant and sensitive advances analysis technologies for real time investigation of CNTs toxicity. Our research aims at elucidating the mechanisms involved in CNTs internalization and association with cellular systems by evaluating the overall effects on of CNTs on cellular biophysical properties-biomechanics. To unravel the biomolecular mechanisms of such interactions, we used Fluorescence Activated Cell Sorting (FACS) and...
The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial p... more The toxicity of engineered nanomaterials in biological systems depends on both the nanomaterial properties and the exposure duration.
Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their im... more Despite the intriguing potential of carbon nanotubes (CNTs) for biomedical applications, their implementation is currently being hindered by many uncertainties regarding their toxicity and fate inside the biological systems. Several reports have shown that CNTs toxicity can be attributed to their length, surface chemistry, aggregation and metal impurities, just to name a few. However, due to the various types of CNTs being synthesized every day along with the different surface functionalization techniques, there is no fundamental understanding of the toxicological and pharmacological profiles of cellular systems exposed to CNTs with different physico-chemical properties. In this research, we provide a comprehensive analysis of the cellular behavior of human lung cells post exposure to CNTs using a combination of electronic and cell-based techniques. Our analyses rely on a non-invasive electronic cell impedance sensing (ECIS) platform to provide real-time measurements of cell adhesio...
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Papers by Reem Eldawud