Rachela Popovtzer - Academia.edu (original) (raw)

Papers by Rachela Popovtzer

Head & neck, 2018

The purpose of this study was to develop a nanoplatform, which simultaneously acts as radiosensit... more The purpose of this study was to develop a nanoplatform, which simultaneously acts as radiosensitizer, drug carrier, and tumor imaging agent for head and neck cancer. We synthesized 20 nm gold nanoparticles, coated with glucose and cisplatin (CG-GNPs). Their penetration into tumor cells and their cellular toxicity were evaluated in vitro. In vivo experiments were conducted to evaluate their impact on tumor growth and their imaging capabilities. The CG-GNPs showed efficient penetration into tumor cells and similar cellular toxicity as cisplatin alone. Combined with radiation, CG-GNPs led to greater tumor reduction than that of radiation alone and radiation with free cisplatin. The CG-GNPs also demonstrated efficient tumor imaging capabilities. Our CG-GNPs have a great potential to increase antitumor effect, overcome resistance to chemotherapeutics and radiation, and allow imaging-guided therapy.

Nanomedicine: Nanotechnology, Biology and Medicine, 2017

Nanomedicine, 2017

Aim: Our goal was to develop an efficient nanoparticle-based system that can overcome the restric... more Aim: Our goal was to develop an efficient nanoparticle-based system that can overcome the restrictive mechanism of the blood–brain barrier (BBB) by targeting insulin receptors and would thus enable drug delivery to the brain. Methods: Insulin-coated gold nanoparticles (INS-GNPs) were synthesized to serve as a BBB transport system. The effect of nanoparticle size (20, 50 and 70 nm) on their ability to cross the BBB was quantitatively investigated in Balb/C mice. Results: The most widespread biodistribution and highest accumulation within the brain were observed using 20 nm INS-GNPs, 2 h post injection. In vivo CT imaging revealed that particles migrated to specific brain regions, which are involved in neurodegenerative and neuropsychiatric disorders. Conclusion: These findings promote the optimization of nanovehicles for transport of drugs through the BBB. The insulin coating of the particles enabled targeting of specific brain regions, suggesting the potential use of INS-GNPs for de...

ACS nano, Jan 11, 2015

Application of immune cell-based therapy in routine clinical practice is challenging due to the p... more Application of immune cell-based therapy in routine clinical practice is challenging due to the poorly understood mechanisms underlying success or failure of treatment. Development of accurate and quantitative imaging techniques for noninvasive cell tracking can provide essential knowledge for elucidating these mechanisms. We designed a novel method for longitudinal and quantitative in vivo cell tracking, based on the superior visualization abilities of classical X-ray computed tomography (CT), combined with state-of-the-art nanotechnology. Herein, T-cells were transduced to express a melanoma-specific T-cell receptor and then labeled with gold nanoparticles (GNPs) as a CT contrast agent. The GNP-labeled T-cells were injected intravenously to mice bearing human melanoma xenografts, and whole-body CT imaging allowed examination of the distribution, migration, and kinetics of T-cells. Using CT, we found that transduced T-cells accumulated at the tumor site, as opposed to nontransduced...

Contrast Media & Molecular Imaging, 2014

Gold nanoparticles have emerged as some of the most extensively utilized nanoplatforms for the di... more Gold nanoparticles have emerged as some of the most extensively utilized nanoplatforms for the diagnosis, imaging, monitoring and treatment of malignant diseases. In particular, in computed tomography (CT) imaging and in therapy (PTT), the exploitation of the various, advantageous properties of gold nanoparticles have resulted in numerous advances in each of these fields. The purpose of this review is to assess the status of gold-nanoparticle mediated CT and PTT, highlight several promising outcomes and motivate the combination of these two functionalities in the same nanoparticle platform. The given examples of research based advances and the encouraging results of in vitro and in vivo studies provide much excitement and promise for future theranostic (therapy + diagnostic) clinical applications, as well as for image-guided therapy and/or surgery, and their monitoring.

Nanomedicine, 2012

The importance of computed tomography (CT) as one of the leading radiology technologies applied i... more The importance of computed tomography (CT) as one of the leading radiology technologies applied in the field of biomedical imaging escalated the development of nanoparticles as the next generation CT contrast agents. Nanoparticles are expected to play a major role in the future of medical diagnostics due to their many advantages over the conventional contrast agents, such as prolonged blood circulation time, controlled biological clearance pathways and specific molecular targeting capabilities. This paper will describe the basic design principles of nanoparticle-based CT contrast agents and review the state-of-the-art developments and clinical applications of blood pool, passive and active targeting CT contrast agents.

International Journal of Nanomedicine, 2012

Background: One of the critical problems in cancer management is local recurrence of disease. Bet... more Background: One of the critical problems in cancer management is local recurrence of disease. Between 20% and 30% of patients who undergo tumor resection surgery require reoperation due to incomplete excision. Currently, there are no validated methods for intraoperative tumor margin detection. In the present work, we demonstrate the potential use of gold nanoparticles (GNPs) as a novel contrast agent for photothermal molecular imaging of cancer. Methods: Phantoms containing different concentrations of GNPs were irradiated with continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms. Results: The results clearly demonstrate the ability to distinguish between cancerous cells specifically targeted with GNPs and normal cells. This technique, which allows highly sensitive discrimination between adjacent low GNP concentrations, will allow tumor margin detection while the temperature increases by only a few degrees Celsius (for GNPs in relevant biological concentrations). Conclusion: We expect this real-time intraoperative imaging technique to assist surgeons in determining clear tumor margins and to maximize the extent of tumor resection while sparing normal background tissue.

Nano Letters, 2008

X-ray based computed tomography (CT), is among the most convenient imaging/diagnostic tools in ho... more X-ray based computed tomography (CT), is among the most convenient imaging/diagnostic tools in hospitals today in terms of availability, efficiency and cost. However, in contrast to magnetic resonance imaging (MRI) and various nuclear medicine imaging modalities, CT is not considered a molecular imaging modality since targeted and molecularly specific contrast agents have not yet been developed. Here we describe a targeted molecular imaging platform that enables, for the first time, cancer detection at the cellular and molecular level with standard clinical CT. The method is based on gold nano-probes that selectively and sensitively target tumor selective antigens, while inducing distinct contrast in CT imaging (increased x-ray attenuation). We present an in vitro proof of principle demonstration for head and neck cancer, showing that the attenuation coefficient for the molecularly targeted cells is over 5 times higher than for identical but untargeted cancer cells or for normal cells. We expect this novel imaging tool to lead to significant improvements in cancer therapy, due to earlier detection, accurate staging and micro-tumor identification.

Integration of biological substance within electronic devices is an innovative and challenging ar... more Integration of biological substance within electronic devices is an innovative and challenging area combining recent progress in molecular biology and micro technology. First, we introduce the concept of integrating living cells with Micro Electro Mechanical Systems (MEMS). Following a brief overview on “whole cell based biosensors” we describe the design, fabrication, and process of a biocompatible electrochemical “Lab-on-a-Chip” system. Demonstrating the application of electrochemical interfacing based whole cell bio chips, we present two different configurations: a. integration of prokaryotic cells (bacteria) for water toxicity detection, and b. integration of eukaryotic cells (human colon cancer cells) for rapid evaluation of the effectiveness of drug treatments. Both applications, with either microbes or mammalian cells integrated onto MEMS based biochips with liquid volume in the range of 100 nL–1 μL, function well and yield a detectable signal much higher than noise level after few minutes.

Analytical Chemistry, 2006

We describe here a bacterial sensor for electrochemical detection of toxic chemicals. The sensor ... more We describe here a bacterial sensor for electrochemical detection of toxic chemicals. The sensor constitutes recombinant bacteria harboring plasmids encoding the fabA and fabR genes and has high-resolution amperometric response to membrane-damaging chemicals. For example, it can detect phenol at concentrations ranging between 1.6 and 16 ppm within 20 min. The high sensitivity is achieved by using the fabA promoter fused to a reporter gene-encoded beta-galactosidase on a low copy number plasmid, under the control of the FabR repressor. The use of electrochemical whole cell sensors enables sensitive, fast, easy to operate, and cost-effective detection of water toxicity threats.

Nanomedicine-nanotechnology Biology and Medicine, 2008

We describe a new method for rapid, sensitive, and high-throughput detection of colon cancer cell... more We describe a new method for rapid, sensitive, and high-throughput detection of colon cancer cells' response to differentiation therapy, using a novel electrochemical lab-on-a-chip system. Differentiation-inducing agents such as butyric acid and its derivatives were introduced to miniature colon cancer samples within the nanovolume chip chambers. The efficacy of each of the differentiationinducing agents was evaluated by electrochemical detection of the cellular enzymatic activity level, whereas reappearance of normal enzymatic activity denotes effective therapy. The results demonstrate the ability to evaluate simultaneously multiplex drug effects on miniature tumor samples (~15 cells) rapidly (5 minutes) and sensitively, with quantitative correlation between cancer cells' number and the induced current. The use of miniature analytical devices is of special interest in clinically relevant samples, in that it requires less tissue for diagnosis, and enables high-throughput analysis and comparison of various drug effects on one small tumor sample, while maintaining uniform biological and environmental conditions.

Journal of Electroanalytical Chemistry, 2007

Whole cell biosensors, which have been genetically engineered to respond to environmental stress,... more Whole cell biosensors, which have been genetically engineered to respond to environmental stress, trigger a sequence of processes, which leads to generation of electrical current. This work presents a mathematical model describing the kinetic properties of the bacterial ...

Sensors and Actuators B-chemical, 2006

... temperature control and a pocket PC (Palm Instruments BV-2004) for sensing and data analysis.... more ... temperature control and a pocket PC (Palm Instruments BV-2004) for sensing and data analysis. ... in each electrochemical cell in the array on the chip by the potentiostat, and the ... arrays requires additional considerations on the effects that can disrupt high signal integrity like noise ...

Nano Letters, 2005

An electrochemical nano-biochip for water toxicity detection is presented. We describe chip desig... more An electrochemical nano-biochip for water toxicity detection is presented. We describe chip design, fabrication, and performance. Bacteria, which have been genetically engineered to respond to environmental stress, act as a sensor element and trigger a sequence of processes, which leads to generation of electrical current. This novel, portable and miniature device provides rapid and sensitive real-time electrochemical detection of acute toxicity in water. A clear signal is produced within less than 10 min of exposure to various concentrations of toxicants, or to stress conditions, with a direct correlation between the toxicant concentration and the induced current.

Current Pharmaceutical Biotechnology, 2010

Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made... more Whole-cell bio-chips for functional sensing integrate living cells on miniaturized platforms made by microsystem-technologies (MST). The cells are integrated, deposited or immersed in a media which is in contact with the chip. The cells behavior is monitored via electrical, electrochemical or optical methods. In this paper we describe such wholecell biochips where the signal is generated due to the genetic response of the cells. The solid-state platform hosts the biological component, i.e. the living cells, and integrates all the required micro-system technologies, i.e. the microelectronics, micro-electro optics, micro-electro or magneto mechanics and micro-fluidics. The genetic response of the cells expresses proteins that generate: a. light by photo-luminescence or bioluminescence, b. electrochemical signal by interaction with a substrate, or c. change in the cell impedance. The cell response is detected by a front end unit that converts it to current or voltage amplifies and filters it. The resultant signal is analyzed and stored for further processing. In this paper we describe three examples of whole-cell bio chips, photo-luminescent, bioluminescent and electrochemical, which are based on the genetic response of genetically modified E. coli microbes integrated on a micro-fluidics MEMS platform. We describe the chip outline as well as the basic modeling scheme of such sensors. We discuss the highlights and problems of such system, from the point of view of micro-system-technology.

One of the critical problems in cancer management is local recurrence of disease. Between 20% and... more One of the critical problems in cancer management is local recurrence of disease. Between 20% and 30% of patients who undergo tumor resection surgery require reoperation due to incomplete excision. Currently, there are no validated methods for intraoperative tumor margin detection. In the present work, we demonstrate the potential use of gold nanoparticles (GNPs) as a novel contrast agent for photothermal molecular imaging of cancer. Methods: Phantoms containing different concentrations of GNPs were irradiated with continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms.