Thikra Mustafa - Academia.edu (original) (raw)

Papers by Thikra Mustafa

Research paper thumbnail of Iron oxide nanoparticle-based radio-frequency thermotherapy for human breast adenocarcinoma cancer cells

Biomaterials Science, 2013

ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as m... more ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as mediators of thermal cytotoxicity under radio-frequency (RF) exposure. The 25 nm IONPs were found to be the most efficient of the three in killing cancer cells at 350 kHz low-frequency RF irradiation. However, at a higher frequency of 13.56 MHz, 15 nm IONPs produced the highest percentage of cell death. Moreover, the killing effect was concentration-dependent in that a higher concentration of IONPs resulted in increased cellular death. Size-dependent internalization of IONPs in MCF-7 cells was quantified by using inductively coupled-plasma mass spectrometry (ICP-MS). Dark-field microscopy and transmission electron microscopy (TEM) revealed that MCF-7 cells internalize IONPs through endocytosis after 24 hours of incubation. In addition, after RF treatment, the cancer cells underwent the apoptosis process, and the level of reactive oxygen species (ROS) increased significantly after hyperthermia. Scanning electron microscopy (SEM) and TEM further established that the ultrastructure morphological changes in the cancer cells originated from the apoptosis process.

Research paper thumbnail of Comparative study of silver nanoparticle permeation using Side-Bi-Side and Franz diffusion cells

Journal of Nanoparticle Research, 2016

Research paper thumbnail of Supplementary Information for paper Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics. Scientific Reports. 2013

Research paper thumbnail of Iron oxide nanoparticle-based radio-frequency thermotherapy for human breast adenocarcinoma cancer cells

Biomaterials Science, 2013

ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as m... more ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as mediators of thermal cytotoxicity under radio-frequency (RF) exposure. The 25 nm IONPs were found to be the most efficient of the three in killing cancer cells at 350 kHz low-frequency RF irradiation. However, at a higher frequency of 13.56 MHz, 15 nm IONPs produced the highest percentage of cell death. Moreover, the killing effect was concentration-dependent in that a higher concentration of IONPs resulted in increased cellular death. Size-dependent internalization of IONPs in MCF-7 cells was quantified by using inductively coupled-plasma mass spectrometry (ICP-MS). Dark-field microscopy and transmission electron microscopy (TEM) revealed that MCF-7 cells internalize IONPs through endocytosis after 24 hours of incubation. In addition, after RF treatment, the cancer cells underwent the apoptosis process, and the level of reactive oxygen species (ROS) increased significantly after hyperthermia. Scanning electron microscopy (SEM) and TEM further established that the ultrastructure morphological changes in the cancer cells originated from the apoptosis process.

Research paper thumbnail of Multifunctional magnetic nanoparticles for synergistic enhancement of cancer treatment by combinatorial radio frequency thermolysis and drug delivery

Advanced healthcare materials, 2012

Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with control... more Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with controlled sizes ranging from 7 to 9 nm. The additional loading of two anti-cancer drugs, doxorubicin and erlotinib, was achieved through - stacking onto the carbon shells. Controlled release of the drugs was successfully triggered by radio frequency (RF) heating or pH variation. Based on the experimental results, C/Fe MNPs act as heat-inducing agents and are able to thermally destroy cancer cells when RF is applied. It was found that the combination of anti-cancer drugs (in particular a low dose of doxorubicin) and RF treatment demonstrates a synergistic effect in inducing cell death in pancreatic cancer cells. Our findings demonstrate that MNPs can be used as highly efficient multimodal nanocarrier agents for an integrated approach to cancer treatment involving triggered delivery of antineoplastic drugs and RF-induced thermal therapy.

Research paper thumbnail of Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics

Scientific Reports, 2013

Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of... more Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action. V arious nanoparticles have been extensively explored either as imaging contrast agents or as a transformer of various energy modalities (e.g., laser, ultrasound, and radio-waves) to thermal and accompanied phenomena (e.g., nanobubbles, acoustic and shock waves, or nanoparticle explosion) responsible for therapeutic effects or as vehicles for drug delivery 1-11 . In particular, laser-induced photothermal (PT) effects in targeted cells lead to protein denaturation, mechanical membrane damage, and even cell fragmentation . PT effects can also provide controllable drug release from nano-carriers followed by conventional biochemical drug action 11 . However, little progress has been made in the use of nanotechnology to directly activate and/or amplify biochemical drug action.

Research paper thumbnail of Novel Multicomponent and Biocompatible Nanocomposite Materials Based on Few-Layer Graphenes Synthesized on a Gold/Hydroxyapatite Catalytic System with Applications in Bone Regeneration

The Journal of Physical Chemistry C, 2011

... Alexandru R. Biris*†, Meena Mahmood‡, Mihaela D. Lazar†, Enkeleda Dervishi‡, Fumiya ... The A... more ... Alexandru R. Biris*†, Meena Mahmood‡, Mihaela D. Lazar†, Enkeleda Dervishi‡, Fumiya ... The Au target concentration was of 1%. The preparation method and metal concentration were chosen such that a catalyst with very small (3–10 nm) and well-dispersed Au nanoparticles ...

Research paper thumbnail of Carbon Nanotubes as Plant Growth Regulators: Effects on Tomato Growth, Reproductive System, and Soil Microbial Community

Research paper thumbnail of Genotoxicity of TiO2 anatase nanoparticles in B6C3F1 male mice evaluated using Pig-a and flow cytometric micronucleus assays

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2012

In vivo micronucleus and Pig-a (phosphatidylinositol glycan, class A gene) mutation assays were c... more In vivo micronucleus and Pig-a (phosphatidylinositol glycan, class A gene) mutation assays were conducted to evaluate the genotoxicity of 10 nm titanium dioxide anatase nanoparticles (TiO 2 -NPs) in mice. Groups of five 6-7-week-old male B6C3F1 mice were treated intravenously for three consecutive days with 0.5, 5.0, and 50 mg/kg TiO 2 -NPs for the two assays; mouse blood was sampled one day before the treatment and on Day 4, and Weeks 1, 2, 4, and 6 after the beginning of the treatment; Pig-a mutant frequencies were determined at Day −1 and Weeks 1, 2, 4 and 6, while percent micronucleated-reticulocyte (%MN-RET) frequencies were measured on Day 4 only. Additional animals were treated intravenously with three daily doses of 50 mg/kg TiO 2 -NPs for the measurement of titanium levels in bone marrow after 4, 24, and 48 h of the last treatment. The measurement indicated that the accumulation of the nanoparticles reached the peak in the tissue 4 h after the administration and the levels were maintained for a few days. No increase in either Pig-a mutant frequency or the frequency of %MN-RETs was detected, although the %RETs was reduced in the treated animals on Day 4 in a dose-dependent manner indicating cytotoxicity of TiO 2 -NPs in the bone marrow. These results suggest that although TiO 2 -NPs can reach the mouse bone marrow and are capable of inducing cytotoxicity, the nanoparticles are not genotoxic when assessed with in vivo micronucleus and Pig-a gene mutation tests.

Research paper thumbnail of TEM Study of Cellular Uptake of Gold Nanoparticles by MC3T3-E1 Bone Cells

Microscopy and Microanalysis, 2011

Research paper thumbnail of Task-dependence of subjective believability in integration of scientific data

International Journal of Information Quality, 2012

ABSTRACT

Research paper thumbnail of Valved Polytetrafluoroethylene Conduits for Right Ventricular Outflow Tract Reconstruction

The Annals of Thoracic Surgery, 2015

Background. The purposes of this study were to review our early outcomes using valved expanded po... more Background. The purposes of this study were to review our early outcomes using valved expanded polytetrafluoroethylene (ePTFE) conduits, with or without bulging sinus structure, for right ventricular outflow tract reconstruction and to examine the mechanical properties of the ePTFE material after bulging sinuses were created.

Research paper thumbnail of Role of carbonaceous nanomaterials in stimulating osteogenesis in mammalian bone cells

Journal of Materials Chemistry B, 2013

In this work, we demonstrate that graphitic nanomaterials-carboxylated multi-walled carbon nanotu... more In this work, we demonstrate that graphitic nanomaterials-carboxylated multi-walled carbon nanotubes (MWCNTs) and carboxylated graphenes (Gn)-have the ability to stimulate the process of osteogenesis in mammalian bone cells and significantly increase the level of bone mineralization. Exposure of MC3T3-E1 bone cells to carboxylated MWCNTs-nano-sized (nano-Gn) and micro-sized (micro-Gn) in concentrations of 1-10 mg ml À1 -resulted in the enhancement of mineralization in a time-dependent manner for the cells exposed to the nanomaterials, as compared to unexposed cells. However, the graphitic nanomaterials did not show significant toxicity in the concentration levels that were studied. Gene expression analysis revealed that the MWCNTs activated expression of the mid-stage osteogenic marker, Col I, on the 12 th day of cell incubation. The gene expression of the earliest osteogenic marker, Cbfa-1, and the downstream effector of BMP signaling, SMAD1, were significantly increased in bone cells exposed to both materials (MWCNTs and nano-Gn) as compared to unexposed control cells. Our data clearly demonstrate the ability of graphitic nano-materials to penetrate bone cells and regulate deposition of minerals in an in vitro model system. Our findings highlight the potential use of such materials in regenerative nanomedicine.

Research paper thumbnail of Nanodelivery of parthenolide using functionalized nanographene enhances its anticancer activity

RSC Adv., 2014

Advances in anticancer chemotherapy have been hindered by the lack of biocompatibility of new pro... more Advances in anticancer chemotherapy have been hindered by the lack of biocompatibility of new prospective drugs. One significant challenge concerns water insolubility, which compromises the bioavailability of the drugs leading to increased dosage and higher systemic toxicity. To overcome these problems, nanodelivery has been established as a promising approach for increasing the efficacy and lowering the required dosage of chemotherapeutics. The naturally derived compound, parthenolide (PTL), is known for its anti-inflammatory and anticancer activity, but its poor water solubility limits its clinical value. In the present study, we have used carboxyl-functionalized nanographene (fGn) delivery to overcome the extreme hydrophobicity of this drug. A water-soluble PTL analog, dimethylamino parthenolide (DMAPT), was also examined for comparison with the anticancer efficacy of our PTL-fGn complex. Delivery by fGn was found to increase the anticancer/apoptotic effects of PTL (but not DMAPT) when delivered to the human pancreatic cancer cell line, Panc-1. The IC50 value for PTL decreased from 39 µM to 9.5 µM when delivered as a mixture with fGn. The IC50 of DMAPT did not decrease when delivered as DMAPT-fGn and was significantly higher than that for PTL-fGn. There were significant increases in ROS formation and in mitochondrial membrane disruption in Panc-1 cells after PTL-fGn treatment as compared to PTL treatment, alone. Increases in toxicity were also seen with apoptosis detection assays using flow cytometry, ethidium bromide/acridine orange/DAPI staining, and TUNEL. Thus, fGn delivery was successfully used to overcome the poor water solubility of PTL, providing a strategy for improving the effectiveness of this anticancer agent.

Research paper thumbnail of Calcium-channel blocking and nanoparticles-based drug delivery for treatment of drug-resistant human cancers

Therapeutic delivery, 2014

Cancer cell chemoresistance is one of the major limitations to successful cancer treatment and on... more Cancer cell chemoresistance is one of the major limitations to successful cancer treatment and one of the factors that is responsible for the possible recurrence of the disease. Here, we aimed to combine a calcium-channel blocker, verapamil, with an alternative delivery of the anti-cancer drug, doxorubicin, using nanostructural materials. This approach could reduce the cellular resistance to chemotherapeutics agents. The outcome of this complex approach on cellular viability was investigated by using various assays in both a time- and concentration-dependent manner: WST-1, flow cytometry cell viability assay, fluorescence microscopy, DNA fragmentation, and TUNEL labeling of apoptotic cells. All of these analytical assays confirmed the ability to reduce the chemoresistance of the cancer cells based on the proposed procedure.

Research paper thumbnail of Organic/Inorganic Hybrid Photovoltaic Cells Based on Substitutionally Doped Single Wall Carbon Nanotubes

2010 IEEE Industry Applications Society Annual Meeting, 2010

In this work we have reported low cost solar cells which can be processed to scalability by depos... more In this work we have reported low cost solar cells which can be processed to scalability by depositing direct and uniform films using airbrushing, inkjet printing, or spin-coating techniques. We have synthesized single wall carbon nanotubes (SWNTs) by catalytic Chemical Vapor Deposition (cCVD) method, which were subsequently doped with boron for photovoltaic applications. The carbon nanotubes were characterized by Raman

Research paper thumbnail of Single-walled carbon nanotube and graphene nanodelivery of gambogic acid increases its cytotoxicity in breast and pancreatic cancer cells

Journal of Applied Toxicology, 2014

Graphene and single-walled carbon nanotubes were used to deliver the natural low-toxicity drug ga... more Graphene and single-walled carbon nanotubes were used to deliver the natural low-toxicity drug gambogic acid (GA) to breast and pancreatic cancer cells in vitro, and the effectiveness of this complex in suppressing cellular integrity was assessed. Cytotoxicity was assessed by measuring lactate dehydrogenase release, mitochondria dehydrogenase activity, mitochondrial membrane depolarization, DNA fragmentation, intracellular lipid content, and membrane permeability/ caspase activity. The nanomaterials showed no toxicity at the concentrations used, and the antiproliferative effects of GA were significantly enhanced by nanodelivery. The results suggest that these complexes inhibit human breast and pancreatic cancer cells grown in vitro. This analysis represents a first step toward assessing their effectiveness in more complex, targeted, nanodelivery systems.

Research paper thumbnail of Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells

International Journal of Nanomedicine, 2011

Research paper thumbnail of Circulating tumor cell identification by functionalized silver-gold nanorods with multicolor, super-enhanced SERS and photothermal resonances

Scientific reports, 2014

Nanotechnology has been extensively explored for cancer diagnostics. However, the specificity of ... more Nanotechnology has been extensively explored for cancer diagnostics. However, the specificity of current methods to identify simultaneously several cancer biomarkers is limited due to color overlapping of bio-conjugated nanoparticles. Here, we present a technique to increase both the molecular and spectral specificity of cancer diagnosis by using tunable silver-gold nanorods with narrow surface-enhanced Raman scattering (SERS) and high photothermal contrast. The silver-gold nanorods were functionalized with four Raman-active molecules and four antibodies specific to breast cancer markers and with leukocyte-specific CD45 marker. More than two orders of magnitude of SERS signal enhancement was observed from these hybrid nanosystems compared to conventional gold nanorods. Using an antibody rainbow cocktail, we demonstrated highly specific detection of single breast cancer cells in unprocessed human blood. By integrating multiplex targeting, multicolor coding, and multimodal detection, ...

Research paper thumbnail of Co doped ZnO semiconductor materials: structural, morphological and magnetic properties

Central European Journal of Physics, 2011

Structural, morphological and magnetic properties of Zn 1−x Co x O (x = 0 01 and 0 03) powdered m... more Structural, morphological and magnetic properties of Zn 1−x Co x O (x = 0 01 and 0 03) powdered materials are presented. XRD studies reveal a wurtzite-type structure, while the formation of a Co 3 O 4 secondary phase was evidenced by Raman spectroscopy. A ferromagnetic behaviour with low Curie temperature was evidenced by Electron Paramagnetic Resonance (EPR) investigation. We suggest that the origin of the ferromagnetism in Zn 1−x Co x O powders is probably due to the presence of the mixed cation valence of Co ions via a double-exchange mechanism rather than the real doping effect.

Research paper thumbnail of Iron oxide nanoparticle-based radio-frequency thermotherapy for human breast adenocarcinoma cancer cells

Biomaterials Science, 2013

ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as m... more ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as mediators of thermal cytotoxicity under radio-frequency (RF) exposure. The 25 nm IONPs were found to be the most efficient of the three in killing cancer cells at 350 kHz low-frequency RF irradiation. However, at a higher frequency of 13.56 MHz, 15 nm IONPs produced the highest percentage of cell death. Moreover, the killing effect was concentration-dependent in that a higher concentration of IONPs resulted in increased cellular death. Size-dependent internalization of IONPs in MCF-7 cells was quantified by using inductively coupled-plasma mass spectrometry (ICP-MS). Dark-field microscopy and transmission electron microscopy (TEM) revealed that MCF-7 cells internalize IONPs through endocytosis after 24 hours of incubation. In addition, after RF treatment, the cancer cells underwent the apoptosis process, and the level of reactive oxygen species (ROS) increased significantly after hyperthermia. Scanning electron microscopy (SEM) and TEM further established that the ultrastructure morphological changes in the cancer cells originated from the apoptosis process.

Research paper thumbnail of Comparative study of silver nanoparticle permeation using Side-Bi-Side and Franz diffusion cells

Journal of Nanoparticle Research, 2016

Research paper thumbnail of Supplementary Information for paper Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics. Scientific Reports. 2013

Research paper thumbnail of Iron oxide nanoparticle-based radio-frequency thermotherapy for human breast adenocarcinoma cancer cells

Biomaterials Science, 2013

ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as m... more ABSTRACT Iron oxide nanoparticles (IONPs) with diameters of 15, 25, and 41 nm were evaluated as mediators of thermal cytotoxicity under radio-frequency (RF) exposure. The 25 nm IONPs were found to be the most efficient of the three in killing cancer cells at 350 kHz low-frequency RF irradiation. However, at a higher frequency of 13.56 MHz, 15 nm IONPs produced the highest percentage of cell death. Moreover, the killing effect was concentration-dependent in that a higher concentration of IONPs resulted in increased cellular death. Size-dependent internalization of IONPs in MCF-7 cells was quantified by using inductively coupled-plasma mass spectrometry (ICP-MS). Dark-field microscopy and transmission electron microscopy (TEM) revealed that MCF-7 cells internalize IONPs through endocytosis after 24 hours of incubation. In addition, after RF treatment, the cancer cells underwent the apoptosis process, and the level of reactive oxygen species (ROS) increased significantly after hyperthermia. Scanning electron microscopy (SEM) and TEM further established that the ultrastructure morphological changes in the cancer cells originated from the apoptosis process.

Research paper thumbnail of Multifunctional magnetic nanoparticles for synergistic enhancement of cancer treatment by combinatorial radio frequency thermolysis and drug delivery

Advanced healthcare materials, 2012

Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with control... more Few-layer, carbon-coated, iron (C/Fe) magnetic nanoparticles (MNPs) were synthesized with controlled sizes ranging from 7 to 9 nm. The additional loading of two anti-cancer drugs, doxorubicin and erlotinib, was achieved through - stacking onto the carbon shells. Controlled release of the drugs was successfully triggered by radio frequency (RF) heating or pH variation. Based on the experimental results, C/Fe MNPs act as heat-inducing agents and are able to thermally destroy cancer cells when RF is applied. It was found that the combination of anti-cancer drugs (in particular a low dose of doxorubicin) and RF treatment demonstrates a synergistic effect in inducing cell death in pancreatic cancer cells. Our findings demonstrate that MNPs can be used as highly efficient multimodal nanocarrier agents for an integrated approach to cancer treatment involving triggered delivery of antineoplastic drugs and RF-induced thermal therapy.

Research paper thumbnail of Photothermal nanodrugs: potential of TNF-gold nanospheres for cancer theranostics

Scientific Reports, 2013

Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of... more Nanotechnology has been extensively explored for drug delivery. Here, we introduce the concept of a nanodrug based on synergy of photothermally-activated physical and biological effects in nanoparticle-drug conjugates. To prove this concept, we utilized tumor necrosis factor-alpha coated gold nanospheres (Au-TNF) heated by laser pulses. To enhance photothermal efficiency in near-infrared window of tissue transparency we explored slightly ellipsoidal nanoparticles, its clustering, and laser-induced nonlinear dynamic phenomena leading to amplification and spectral sharpening of photothermal and photoacoustic resonances red-shifted relatively to linear plasmonic resonances. Using a murine carcinoma model, we demonstrated higher therapy efficacy of Au-TNF conjugates compared to laser and Au-TNF alone or laser with TNF-free gold nanospheres. The photothermal activation of low toxicity Au-TNF conjugates, which are in phase II trials in humans, with a laser approved for medical applications opens new avenues in the development of clinically relevant nanodrugs with synergistic antitumor theranostic action. V arious nanoparticles have been extensively explored either as imaging contrast agents or as a transformer of various energy modalities (e.g., laser, ultrasound, and radio-waves) to thermal and accompanied phenomena (e.g., nanobubbles, acoustic and shock waves, or nanoparticle explosion) responsible for therapeutic effects or as vehicles for drug delivery 1-11 . In particular, laser-induced photothermal (PT) effects in targeted cells lead to protein denaturation, mechanical membrane damage, and even cell fragmentation . PT effects can also provide controllable drug release from nano-carriers followed by conventional biochemical drug action 11 . However, little progress has been made in the use of nanotechnology to directly activate and/or amplify biochemical drug action.

Research paper thumbnail of Novel Multicomponent and Biocompatible Nanocomposite Materials Based on Few-Layer Graphenes Synthesized on a Gold/Hydroxyapatite Catalytic System with Applications in Bone Regeneration

The Journal of Physical Chemistry C, 2011

... Alexandru R. Biris*†, Meena Mahmood‡, Mihaela D. Lazar†, Enkeleda Dervishi‡, Fumiya ... The A... more ... Alexandru R. Biris*†, Meena Mahmood‡, Mihaela D. Lazar†, Enkeleda Dervishi‡, Fumiya ... The Au target concentration was of 1%. The preparation method and metal concentration were chosen such that a catalyst with very small (3–10 nm) and well-dispersed Au nanoparticles ...

Research paper thumbnail of Carbon Nanotubes as Plant Growth Regulators: Effects on Tomato Growth, Reproductive System, and Soil Microbial Community

Research paper thumbnail of Genotoxicity of TiO2 anatase nanoparticles in B6C3F1 male mice evaluated using Pig-a and flow cytometric micronucleus assays

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 2012

In vivo micronucleus and Pig-a (phosphatidylinositol glycan, class A gene) mutation assays were c... more In vivo micronucleus and Pig-a (phosphatidylinositol glycan, class A gene) mutation assays were conducted to evaluate the genotoxicity of 10 nm titanium dioxide anatase nanoparticles (TiO 2 -NPs) in mice. Groups of five 6-7-week-old male B6C3F1 mice were treated intravenously for three consecutive days with 0.5, 5.0, and 50 mg/kg TiO 2 -NPs for the two assays; mouse blood was sampled one day before the treatment and on Day 4, and Weeks 1, 2, 4, and 6 after the beginning of the treatment; Pig-a mutant frequencies were determined at Day −1 and Weeks 1, 2, 4 and 6, while percent micronucleated-reticulocyte (%MN-RET) frequencies were measured on Day 4 only. Additional animals were treated intravenously with three daily doses of 50 mg/kg TiO 2 -NPs for the measurement of titanium levels in bone marrow after 4, 24, and 48 h of the last treatment. The measurement indicated that the accumulation of the nanoparticles reached the peak in the tissue 4 h after the administration and the levels were maintained for a few days. No increase in either Pig-a mutant frequency or the frequency of %MN-RETs was detected, although the %RETs was reduced in the treated animals on Day 4 in a dose-dependent manner indicating cytotoxicity of TiO 2 -NPs in the bone marrow. These results suggest that although TiO 2 -NPs can reach the mouse bone marrow and are capable of inducing cytotoxicity, the nanoparticles are not genotoxic when assessed with in vivo micronucleus and Pig-a gene mutation tests.

Research paper thumbnail of TEM Study of Cellular Uptake of Gold Nanoparticles by MC3T3-E1 Bone Cells

Microscopy and Microanalysis, 2011

Research paper thumbnail of Task-dependence of subjective believability in integration of scientific data

International Journal of Information Quality, 2012

ABSTRACT

Research paper thumbnail of Valved Polytetrafluoroethylene Conduits for Right Ventricular Outflow Tract Reconstruction

The Annals of Thoracic Surgery, 2015

Background. The purposes of this study were to review our early outcomes using valved expanded po... more Background. The purposes of this study were to review our early outcomes using valved expanded polytetrafluoroethylene (ePTFE) conduits, with or without bulging sinus structure, for right ventricular outflow tract reconstruction and to examine the mechanical properties of the ePTFE material after bulging sinuses were created.

Research paper thumbnail of Role of carbonaceous nanomaterials in stimulating osteogenesis in mammalian bone cells

Journal of Materials Chemistry B, 2013

In this work, we demonstrate that graphitic nanomaterials-carboxylated multi-walled carbon nanotu... more In this work, we demonstrate that graphitic nanomaterials-carboxylated multi-walled carbon nanotubes (MWCNTs) and carboxylated graphenes (Gn)-have the ability to stimulate the process of osteogenesis in mammalian bone cells and significantly increase the level of bone mineralization. Exposure of MC3T3-E1 bone cells to carboxylated MWCNTs-nano-sized (nano-Gn) and micro-sized (micro-Gn) in concentrations of 1-10 mg ml À1 -resulted in the enhancement of mineralization in a time-dependent manner for the cells exposed to the nanomaterials, as compared to unexposed cells. However, the graphitic nanomaterials did not show significant toxicity in the concentration levels that were studied. Gene expression analysis revealed that the MWCNTs activated expression of the mid-stage osteogenic marker, Col I, on the 12 th day of cell incubation. The gene expression of the earliest osteogenic marker, Cbfa-1, and the downstream effector of BMP signaling, SMAD1, were significantly increased in bone cells exposed to both materials (MWCNTs and nano-Gn) as compared to unexposed control cells. Our data clearly demonstrate the ability of graphitic nano-materials to penetrate bone cells and regulate deposition of minerals in an in vitro model system. Our findings highlight the potential use of such materials in regenerative nanomedicine.

Research paper thumbnail of Nanodelivery of parthenolide using functionalized nanographene enhances its anticancer activity

RSC Adv., 2014

Advances in anticancer chemotherapy have been hindered by the lack of biocompatibility of new pro... more Advances in anticancer chemotherapy have been hindered by the lack of biocompatibility of new prospective drugs. One significant challenge concerns water insolubility, which compromises the bioavailability of the drugs leading to increased dosage and higher systemic toxicity. To overcome these problems, nanodelivery has been established as a promising approach for increasing the efficacy and lowering the required dosage of chemotherapeutics. The naturally derived compound, parthenolide (PTL), is known for its anti-inflammatory and anticancer activity, but its poor water solubility limits its clinical value. In the present study, we have used carboxyl-functionalized nanographene (fGn) delivery to overcome the extreme hydrophobicity of this drug. A water-soluble PTL analog, dimethylamino parthenolide (DMAPT), was also examined for comparison with the anticancer efficacy of our PTL-fGn complex. Delivery by fGn was found to increase the anticancer/apoptotic effects of PTL (but not DMAPT) when delivered to the human pancreatic cancer cell line, Panc-1. The IC50 value for PTL decreased from 39 µM to 9.5 µM when delivered as a mixture with fGn. The IC50 of DMAPT did not decrease when delivered as DMAPT-fGn and was significantly higher than that for PTL-fGn. There were significant increases in ROS formation and in mitochondrial membrane disruption in Panc-1 cells after PTL-fGn treatment as compared to PTL treatment, alone. Increases in toxicity were also seen with apoptosis detection assays using flow cytometry, ethidium bromide/acridine orange/DAPI staining, and TUNEL. Thus, fGn delivery was successfully used to overcome the poor water solubility of PTL, providing a strategy for improving the effectiveness of this anticancer agent.

Research paper thumbnail of Calcium-channel blocking and nanoparticles-based drug delivery for treatment of drug-resistant human cancers

Therapeutic delivery, 2014

Cancer cell chemoresistance is one of the major limitations to successful cancer treatment and on... more Cancer cell chemoresistance is one of the major limitations to successful cancer treatment and one of the factors that is responsible for the possible recurrence of the disease. Here, we aimed to combine a calcium-channel blocker, verapamil, with an alternative delivery of the anti-cancer drug, doxorubicin, using nanostructural materials. This approach could reduce the cellular resistance to chemotherapeutics agents. The outcome of this complex approach on cellular viability was investigated by using various assays in both a time- and concentration-dependent manner: WST-1, flow cytometry cell viability assay, fluorescence microscopy, DNA fragmentation, and TUNEL labeling of apoptotic cells. All of these analytical assays confirmed the ability to reduce the chemoresistance of the cancer cells based on the proposed procedure.

Research paper thumbnail of Organic/Inorganic Hybrid Photovoltaic Cells Based on Substitutionally Doped Single Wall Carbon Nanotubes

2010 IEEE Industry Applications Society Annual Meeting, 2010

In this work we have reported low cost solar cells which can be processed to scalability by depos... more In this work we have reported low cost solar cells which can be processed to scalability by depositing direct and uniform films using airbrushing, inkjet printing, or spin-coating techniques. We have synthesized single wall carbon nanotubes (SWNTs) by catalytic Chemical Vapor Deposition (cCVD) method, which were subsequently doped with boron for photovoltaic applications. The carbon nanotubes were characterized by Raman

Research paper thumbnail of Single-walled carbon nanotube and graphene nanodelivery of gambogic acid increases its cytotoxicity in breast and pancreatic cancer cells

Journal of Applied Toxicology, 2014

Graphene and single-walled carbon nanotubes were used to deliver the natural low-toxicity drug ga... more Graphene and single-walled carbon nanotubes were used to deliver the natural low-toxicity drug gambogic acid (GA) to breast and pancreatic cancer cells in vitro, and the effectiveness of this complex in suppressing cellular integrity was assessed. Cytotoxicity was assessed by measuring lactate dehydrogenase release, mitochondria dehydrogenase activity, mitochondrial membrane depolarization, DNA fragmentation, intracellular lipid content, and membrane permeability/ caspase activity. The nanomaterials showed no toxicity at the concentrations used, and the antiproliferative effects of GA were significantly enhanced by nanodelivery. The results suggest that these complexes inhibit human breast and pancreatic cancer cells grown in vitro. This analysis represents a first step toward assessing their effectiveness in more complex, targeted, nanodelivery systems.

Research paper thumbnail of Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells

International Journal of Nanomedicine, 2011

Research paper thumbnail of Circulating tumor cell identification by functionalized silver-gold nanorods with multicolor, super-enhanced SERS and photothermal resonances

Scientific reports, 2014

Nanotechnology has been extensively explored for cancer diagnostics. However, the specificity of ... more Nanotechnology has been extensively explored for cancer diagnostics. However, the specificity of current methods to identify simultaneously several cancer biomarkers is limited due to color overlapping of bio-conjugated nanoparticles. Here, we present a technique to increase both the molecular and spectral specificity of cancer diagnosis by using tunable silver-gold nanorods with narrow surface-enhanced Raman scattering (SERS) and high photothermal contrast. The silver-gold nanorods were functionalized with four Raman-active molecules and four antibodies specific to breast cancer markers and with leukocyte-specific CD45 marker. More than two orders of magnitude of SERS signal enhancement was observed from these hybrid nanosystems compared to conventional gold nanorods. Using an antibody rainbow cocktail, we demonstrated highly specific detection of single breast cancer cells in unprocessed human blood. By integrating multiplex targeting, multicolor coding, and multimodal detection, ...

Research paper thumbnail of Co doped ZnO semiconductor materials: structural, morphological and magnetic properties

Central European Journal of Physics, 2011

Structural, morphological and magnetic properties of Zn 1−x Co x O (x = 0 01 and 0 03) powdered m... more Structural, morphological and magnetic properties of Zn 1−x Co x O (x = 0 01 and 0 03) powdered materials are presented. XRD studies reveal a wurtzite-type structure, while the formation of a Co 3 O 4 secondary phase was evidenced by Raman spectroscopy. A ferromagnetic behaviour with low Curie temperature was evidenced by Electron Paramagnetic Resonance (EPR) investigation. We suggest that the origin of the ferromagnetism in Zn 1−x Co x O powders is probably due to the presence of the mixed cation valence of Co ions via a double-exchange mechanism rather than the real doping effect.