“Nano-Taxis” Shuttle Therapeutics to Neurons

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“Nano-Taxis” Shuttle Therapeutics to Neurons

Technion scientists create innovative “nano-taxis,” capable of shuttling therapeutics directly to neurons, paving the way for treatment of neurodegenerative diseases and traumatic brain injuries

Assistant Professor Assaf Zinger

Technion – Israel Institute of Technology Assistant Professor Assaf Zinger and Dr. Caroline Cvetkovic from the Center for Neuroregeneration at the Houston Methodist Research Institute have created a novel means of delivering medicine to neurons in a targeted manner. They developed biomimetic nano-vesicles, or nature-mimicking, nanometer-scale “vehicles,” capable of specifically targeting neurons (i.e., nerve) cells. This tool paves the way for the treatment of multiple neurodegenerative diseases and traumatic brain injuries.

Their findings were recently published in Advanced Science.

Drug delivery is a major challenge that must be overcome in drug development, and it is one of the focus areas of the Wolfson Faculty of Chemical Engineering at the Technion. It is not enough that a substance can lead to the desired therapeutic effect in a specific cell. This therapeutic substance must also reach these cells without being changed or destroyed en route, and it must not end up in other organs if it might cause harm there.

“Neurosomes”- Humanized Biomimetic nano vesicles (red) for neuron targeting (green)

In explaining what led him to this study, Dr. Zinger said, “One Saturday, my family and I were dining with friends. Their little girl has a neurodegenerative disorder; she can’t speak and has a motor disorder. I wanted to help her.”

Dr. Zinger was already working on various types of biomimetic nano-vesicles. These nano-vesicles are similar in their basic structure to human cells but much smaller – one millionth of a hair’s width in diameter. They can carry within them cargo that needs to be delivered to the cells – medication, mRNA, etc.

The targeting of these nano-vesicles is achieved by incorporating specific cell membrane-derived proteins on their surface, thus letting them be recognized and taken in by the correct cells. These specific proteins that cover the surface of these nano-vesicles are naturally used by the body to identify its cells and this is what biomimicry is all about. In essence, the nano vesicles (or taxis) masquerade as neurons, resulting in their being recognized and welcomed by other neurons, thereby making it possible for them to deliver their therapeutic cargo.

Potentially revolutionizing the treatment of neurodegenerative disorders and traumatic brain injuries

These findings have broad implications. More than one neurodegenerative disorder might be treated if the correct medicine or genetic cargo (e.g., mRNA, SiRNA, miRNA) could be delivered to the brain. But these are not the only possible applications. “With this, we can also potentially revolutionize the treatment of traumatic brain injuries,” Prof. Zinger explained. “In the case of a car accident and or a sports injury, as examples, the brain is first damaged by the impact, as it is struck against the skull. As a result, multiple brain cells are damaged. This starts a process of inflammation. If we could immediately deliver anti-inflammatory drugs to the brain, we could reduce the inflammatory processes, and hopefully prevent fatalities and long-term disabilities.”

The lion’s share of this study was conducted by Dr. Zinger at the Houston Methodist Research Institute and Houston Methodist Hospital as part of his postdoctoral fellowship. Dr. Zinger recently opened a multidisciplinary laboratory at the Technion, in the Wolfson Faculty of Chemical Engineering. His lab aims to create advanced bioinspired technologies and translational therapeutics through a highly multidisciplinary approach. Specifically, Dr. Zinger’s group will integrate in vitro and in vivo models with imaging, molecular biology, and chemical techniques to design novel nano-based technologies that will achieve organ- and cell-specific targeting for improved therapeutic outcomes in different brain and neural diseases, injuries, and various cancers.

To read the full article, click here.

Cancer Cells Mobilizing the Nervous System? Let’s Use Them to Inhibit the Tumor

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Cancer Cells Mobilizing the Nervous System? Let’s Use Them to Inhibit the Tumor

October is Breast Cancer Awareness Month, and Technion researchers have just published findings in Science Advances that support the efficacy of the technology that they developed: Treatment of breast cancer by anesthesia of the nervous system around the tumor. The treatment not only inhibited tumor growth but also prevented metastasis to other organs                                                                                                

Professor Avi Schroeder

Researchers at the Technion – Israel Institute of Technology have developed an innovative treatment for breast cancer, based on analgesic nanoparticles that target the nervous system. The study, published in Science Advances, was led by Professor Avi Schroeder and Ph.D. student Maya Kaduri of the Wolfson Faculty of Chemical Engineering.

Breast cancer is one of the most common cancers in women, and despite breakthroughs in diagnosis and treatment, about one thousand women in Israel die of the disease per year. Around 15% of them are under the age of 50. Worldwide, some 685,000 women die each year from breast cancer.

Prof. Schroeder has years of experience in developing innovative cancer treatments, including ones for breast cancer and specifically triple-negative breast cancer – an aggressive cancer characterized by rapid cell division with a higher risk of metastasis. Technologies developed in his lab include novel methods for encapsulating drug molecules in nanoparticles that transport the drug to the tumor and release it inside, without damaging healthy tissue.

The researchers found that cancer cells have a reciprocal relationship with the nerve cells around them: the cancer cells stimulate infiltration of nerve cells into the tumor, and this infiltration stimulates cancer cell proliferation, growth, and migration. In other words, the cancer cells recruit the nerve cells for their purposes.

Based on these findings, the researchers developed a treatment that targets the tumor through the nerve cells. This treatment is based on injecting nanoparticles containing anesthetic into the bloodstream. The nanoparticles travel through the bloodstream toward the tumor, accumulate around the nerve cells in the cancerous tissue, and paralyze the local nerves and communication between the nerve cells and the cancer cells. The result: significant inhibition of tumor development and of metastasis to the lungs, brain, and bone marrow.

The nanoparticles simulate the cell membrane and are coated with special polymers that disguise them from the immune system and enable a long circulation time in the bloodstream. Each such particle, which is around 100 nm in diameter, contains the anesthetic.

Maya Kaduri

According to Maya Kaduri: “We know how to create the exact size of particles needed, and that is critical because it’s the key to penetrating the tumor. Tumors stimulate increased formation of new blood vessels around them, so that they receive oxygen and nutrients, but the structure of these blood vessels is damaged and contains nano-sized holes that enable penetration of nanoparticles. The cancerous tissue is characterized by poor lymphatic drainage, which further increases accumulation of the particles in the tissue. Therefore, the anesthetizing particles we developed move through the bloodstream without penetrating healthy tissue. Only when they reach the damaged blood vessels of the tumor do they leak out, accumulate around the nerve cells of the cancerous tissue, and disconnect them from the cancer cells. The fact that this is a very focused and precise treatment enables us to insert significant amounts of anesthetic into the body because there is no fear that it will harm healthy and vital areas of the nervous system.”

In experiments on cancer cell cultures and in treatment of mice, the new technology inhibited not only tumor development but also metastasis. The researchers estimate these findings may be relevant for treatment of breast cancer in humans.

The research is supported by the Rappaport Technion Integrated Cancer Center (RTICC) as part of the Steven & Beverly Rubenstein Charitable Foundation Fellowship Fund for Cancer Research, and by Teva, as part of its National Forum for BioInnovators. The research was conducted in cooperation with the Faculty of Medicine at Hebrew University of Jerusalem and the Institute of Pathology at the Tel Aviv Sourasky Medical Center.

Prof. Avi Schroeder is head of the Louis Family Laboratory for Targeted Drug Delivery & Personalized Medicine Technologies at the Wolfson Faculty of Chemical Engineering. Maya Kaduri, who has a B.Sc. from the Faculty of Biotechnology and Food Engineering at the Technion, began researching under the guidance of Prof. Avi Schroeder during her bachelor’s degree, and this year she is expected to complete her Ph.D. (direct track).

For the article in Science Advances click here

Click here for video demonstrating the research

 

Canadian Making Waves

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Making Desalinated Water Safer and Cheaper

Technion, Wageningen University and Wetsus scientists develop an effective and low-cost way to remove toxic boron from water in the process of desalination

Canadian born, Professor Matthew Suss

80% of drinking water in Israel is desalinated water, coming from the Mediterranean Sea. Now, scientists from the Technion – Israel Institute of Technology, the Wageningen University, and Wetsus (European center of excellence for sustainable water) in the Netherlands have developed a way to improve the quality of desalinated water, while reducing the costs of the process. The findings of the international team’s study were published in PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Amit Shocron

Desalination is the process that removes mineral particles (salts) from saltwater, making it fit for human consumption and for irrigation. The chemical properties of some particles make them more challenging to remove than others. Boron, which is naturally found in high quantities in the Mediterranean Sea, is among the hardest to remove, as change in acidity causes it to change its properties. It is toxic in high concentrations, and it harms plant growth, which is a problem in the context of irrigation. The normal process of boron removal involves dosing the water with a base in order to facilitate removing the boron, followed by removal of the base.

Process of dissolved boron removal using a capacitive deionization cell. First, the cell dissociates boric acid to charged boron ions. The boron ions are then stored in the electrodes. )Credit: Paul Gerlach, Houten, The Netherlands(

The most commonly used method of desalination is by means of a membrane – a sort of sieve that allows water to pass through it, while blocking other particles, based on their size or charge. This membrane, however, is expensive, and needs to be replaced periodically.

Eric Guyes

Ph.D. students Amit Shocron and Eric Guyes, under the supervision of  Canadian born, Professor Matthew Suss of the Technion Faculty of Mechanical Engineering, together with their collaborators from Wageningen University and Wetsus, developed a new modeling technique to predict the behavior of boron during desalination by means of capacitive deionization. This is an emerging technique for water treatment and desalination using relatively cheap porous electrodes, as opposed to the expensive membrane. When an electric current is applied, charged particles (like boron under high pH conditions) are adsorbed by the electrodes and hence removed from the water.

Schematic demonstrating boron removal by a capacitive deionization (CDI) cell. Shown is a CDI cell with an anode placed upstream and a snapshot of the developed pH profile within the anode. Right: A snapshot of ion and charge distributions in a pore near the anode/separator interface, showing boric acid dissociation and adsorption

Amit Shocron formulated the theoretical framework that allowed this breakthrough, while Eric Guyes constructed the experimental setup. Working together, they were able to develop the novel system. They found that for optimal boron removal, the positive electrode should be placed upstream of the negative electrode – counter to the accepted wisdom in their field. They also calculated the optimal applied voltage for the system, finding that higher voltage does not necessarily improve the system’s effectiveness.

This same method the group developed could be used to solve other water treatment challenges as well, for example the removal of medicine residues and herbicides, which are difficult to remove using conventional methods.

Montreal native, Prof. Suss is an Associate Professor in the Faculty of Mechanical Engineering and the Wolfson Department of Chemical Engineering at Technion – Israel Institute of Technology and is affiliated with the Nancy and Stephen Grand Technion Energy Program and Stephen and Nancy Grand Water Research Institute at Technion.

For the article in PNAS click here

 

Dislocations in Gold as an “Autocatalytic Template” for Nanowire Growth

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Dislocations in Gold as an “Autocatalytic Template” for Nanowire Growth

Researchers at the Technion Faculty of Materials Science and Engineering have developed an innovative method for the creation of nanowires with numerous potential applications

Professor Boaz Pokroy

Technion researchers have presented an innovative method for the formation of nanowires. In it, the nanowires form within line defects that exist in metals. Such defects are known as dislocations. This is the first time that dislocation lines in a material of one kind serve as a template for the growth of a different inorganic material in the form of nanowires. The study, which was published in PNAS, was led by Professor Boaz Pokroy and Ph.D. student Lotan Portal of the Faculty of Materials Science and Engineering and the Russell Berrie Nanotechnology Institute (RBNI).

Dislocations are a significant phenomenon in materials science since they affect the material’s properties on both the macro- and microscales. For example, a high dislocation density increases a metal’s strength and hardness. The

Lotan Portal

dislocation edges on metal surfaces and the atoms in their proximity tend to be more chemically activated compared to other atoms in the material and tend to facilitate various chemical reactions, such as corrosion and catalysis.

The researchers in Prof. Pokroy’s group created nanowires of gold-cyanide complex from classic Au-Ag alloy. In professional terminology, they synthesized inorganic gold(I)-cyanide (AuCN) systems in the shape of nanowires, using an autocatalytic reaction (i.e. through the acceleration of a reaction by one of its reactants). Gold-cyanide complex is used in numerous fields including ammonia gas detection (NH3 sensors), catalysis (acceleration) of water-splitting reactions, and others.

Scanning electron microscope image of a lateral section of a sample that contains a gold-cyanide nanowire created from Au-Ag (to a depth of 2 microns from the surface of the sample).

In the process developed by the researchers, nanowires crystallize at the dislocation ends on the surface of the original gold-silver (Au-Ag) alloy, and the final structure obtained is classic nanoporous (sponge-like) gold, with a layer of nanowires emerging from it. Formation of the nanowires occurs during the classic selective dealloying process that separates the silver from the system and forms the nanoporous gold and is achieved only when the dislocation density exceeds a critical value, as presented in the kinetic model developed and demonstrated in the article.

A schematic drawing depicting 1D nucleation and growth of a gold-cyanide nanowire along a dislocation in the original alloy during the classic selective dealloying process.

The model provides a possible route for growing one-dimensional inorganic complexes while controlling the growth direction, shape, and morphology of a crystal according to the original alloy’s slip system. As mentioned, this scientific and technological achievement has numerous potential applications.

The research was sponsored by a European Research Council (ERC) Proof of Concept Grant (“np-Gold” project) as part of the Horizon 2020 Program.

For the article in PNAS click here

 

Journey to the target tissue

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Journey to the target tissue

Computer science in the service of medicine: Researchers at the Technion and the University of North Carolina present an innovative algorithm that safely and efficiently steers curved surgical needles inside the body while avoiding damage to tissue

Researchers from the Technion and the University of North Carolina (UNC) have developed an algorithm that steers surgical needles along 3D curvilinear trajectories. The researchers – Dr. Oren Salzman of the Taub Faculty of Computer Science at the Technion and Prof. Ron Alterovitz and Mengyu Fu of UNC – announced the development at the recently held virtual 2021 Robotics: Science and Systems Conference.

Dr. Oren Salzman

Numerous medical procedures, such as biopsies and localized therapy delivery for cancer, require that a needle be steered safely through tissue, to the target. Straight needles can “get the job done” when the straight path from the point of entry to the target tissue does not pass through vulnerable tissue, but in many cases, the target tissue is “hidden” behind a bone or vulnerable tissue, and in these cases, the surgeon must avoid anatomical obstacles, a difficult, complex task, most certainly when the body parts involved are vulnerable and sensitive.

Against this backdrop, in recent years, medical needles with bevel tips were developed. These needles are controlled by rotating them at their base. The problem is that directing these needles is neither simple nor intuitive, and steering them manually involves numerous risks. This has led to the development of “motion planning algorithms” designed to accurately and safely direct the needle. These algorithms have displayed impressive capabilities, and yet, since these are invasive procedures, the degree of precision required is very high; otherwise, the systems will not be granted regulatory approval.

The development presented by the researchers at the conference illustrates the importance of computer science in solving problems related to medicine and biomedical engineering. On the basis of relevant medical images such as a computed tomography (CT) or magnetic resonance imaging (MRI) scan, the new algorithm computes the optimal trajectory that will lead the needle to the target while avoiding damage to various anatomical obstacles. As opposed to existing algorithms, the new algorithm provides a “completeness” guarantee that the needle can indeed reach the specified target while avoiding those tissues, and if no such safe motion plan exists, it will inform the user accordingly. Moreover, it computes plans faster compared to rival steerable needle motion planners and with a higher success rate. According to the researchers, the technology presented at the conference is a new algorithmic foundation that is expected to lead to additional applications based on automated steerable needles.

Three views of the lung environment. The needle steers to targets (green) while avoiding anatomical obstacles including large blood vessels (red), bronchial tubes (brown), and the lung boundary (gray)

The research was funded by the US National Institutes of Health (NIH), the Israeli Ministry of Science and Technology, and the US-Israel Binational Science Foundation (BSF).

Dr. Oren Salzman joined the Technion staff in the summer of 2019 following a postdoctoral fellowship in the Robotics Institute at Carnegie Mellon University. He is head of the Computational Robotics Lab (CRL) in the Taub Faculty of Computer Science.

German Chancellor Dr. Angela Merkel to Receive an Honorary Doctorate from the Technion

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German Chancellor Dr. Angela Merkel to Receive an Honorary Doctorate from the Technion

The ceremony will take place in Jerusalem, as part of Merkel’s visit to Israel ▪ She will be awarded for her support of Israel, her unwavering fight against antisemitism, and for her strong support of science and education ▪ Technion President Prof. Uri Sivan: “Dr. Merkel is a true leader, constantly striving to improve the lives of millions worldwide”

Bundeskanzlerin Angela Merkel.

Haifa, Israel, October 6, 2021German Chancellor Dr. Angela Merkel will receive an honorary doctorate from the Technion – Israel Institute of Technology in a ceremony set for Oct. 10, 2021, in Jerusalem, Israel.

Chancellor Merkel, who is visiting Israel (after postponing her August 2021 visit), will be awarded for her continuous and steadfast support of the State of Israel; her unwavering fight against antisemitism and racism; her strong support of science and education, and particularly of scientific collaboration between Germany and Israel; and for her exemplary leadership, wisdom, and humanity.

A scientist with a doctoral degree in natural sciences from the German Academy of Sciences in Berlin, Merkel published several papers on quantum chemistry prior to embarking on a political career. She’s set to retire from politics this month, having been in office for 16 years.

“Chancellor Merkel’s path has taken her from a brilliant scientific career in quantum chemistry to an unparalleled political legacy at a time of tectonic changes starting with the end of the Cold War, the fall of the Soviet Union, and the unification of Germany,” said Technion President Prof. Uri Sivan.  “Under her leadership, Merkel navigated Europe through a global economic crisis and displayed great humanity to those who were displaced by civil wars and other armed conflicts in the Middle East and Africa.”

He went on to say that “as a true leader, constantly striving to improve the lives of millions worldwide, Chancellor Merkel never avoided publicly facing the harsh and uncomfortable realities of global and domestic challenges. She has done so while never forgetting the true meaning of compassion and social responsibility.”

Prof. Sivan thanked Chancellor Merkel: “We salute you for what you have given Germany, Israel, and the world. We are forever grateful.”

On Sunday, the Chancellor will receive the honorary doctorate from Prof. Sivan, in the presence of Mr. Gideon Frank, Chairman of the Technion Council; Prof. Oded Rabinovitch, Senior Executive Vice President and a Professor at the Faculty of Civil and Environmental Engineering; Prof. Alon Wolf, Vice President for External Relations and Resource Development and a Professor at the Faculties of Mechanical Engineering and Biomedical Engineering; Distinguished Professor Yitzhak Apeloig, former Technion President and Professor at the Schulich Faculty Of Chemistry; former Technion President Prof. Peretz Lavie, Chairman of Israel Friends of Technion; Nobel Prize Laureate and Technion Distinguished Professor Aaron Ciechanover of the Ruth and Bruce Rappaport Faculty of Medicine; Prof. Marcelle Machluf, Dean of the Faculty of Biotechnology and Food Engineering; as well as graduate students Ms. Lina Muadlej of the Andrew and Erna Viterbi Faculty of Electrical and Computer Engineering (in a joint track with the Henry and Marilyn Taub Faculty of Computer Science), and Ms. Aseel Shomar, a Ph.D. student at the Wolfson Faculty of Chemical  Engineering.

An honorary doctorate is the highest honor bestowed by the Technion – Israel Institute of Technology upon the few who distinguished themselves through their outstanding scientific work or their leadership and public service to the benefit of Israel, the Jewish people, and humanity at large. Some notable examples include Chaim Weizmann (1952), Albert Einstein (1953), Niels Bohr (1958), David Ben Gurion (1962), Yitzhak Rabin (1990), and Margaret Thatcher (1989) – who are now joined by Chancellor Merkel, arguably the most revered, influential leader of our time.

Born in 1954, Chancellor Merkel started her political career in 1989, following the fall of the Berlin Wall. She chaired the Christian Democratic Union Party from 2000-2018; and has served as Chancellor of the Federal Republic of Germany since 2005. Throughout her career, Merkel emphasized international cooperation. She has been described as the de facto leader of the European Union. The New York Times dubbed her “The Liberal West’s Last Defender.” Merkel has voiced support for Israel on many occasions and has spoken out against antisemitism. Congratulating the new Israeli government in June 2021, Merkel said that Germany and Israel are “connected by a unique friendship that we want to further strengthen.”

Photo Credit : Bundespresseamt/Federal Press Office

Revving Up-Formula Racing

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 Revving Up

 Israel’s Formula student teams – absent from international competitions for two years because of COVID-19 – have established their own Formula Race for students

This year’s Technion team is its largest ever

This month, three universities will participate in the inaugural Israeli Formula SAE Race: The Technion – Israel Institute of Technology, Tel Aviv University, and Ben-Gurion University of the Negev.

The Technion team with the 2021 model

The Technion Formula Student Team has been led by the Faculty of Mechanical Engineering since 2013. Academic guidance is provided by Prof. Leonid Tartakovsky, who replaced Prof. Reuven Katz, the project supervisor from 2013 to 2019.

Headed by Muans Omari, a master’s student in the Faculty of Mechanical Engineering, this year’s Technion team is its largest ever, made up of more than 60 students from various faculties. This is Omari’s third year participating in the project; he started out as a volunteer and driver, subsequently progressed to head of the engine crew, and since 2021, has served as the Technion’s project lead. As a driver, he won first place driving on the figure-8 Skidpad circuit in the Czech Republic in the summer of 2019, just before the global COVID-19 outbreak. During that race, the Technion unveiled the lightest car in the history of the competition, which weighed in at just 132 kg of advanced technology, after “Technion Formula” shed 120 kg in just three years.

The Formula cars from the Technion – Israel Institute of Technology, Tel Aviv University, and Ben-Gurion University of the Negev

“After two years in which we were prevented from participating in races in Europe because of the pandemic, we decided to bring the race to Israel,” said Omari, “and the three universities that will be competing in October – the Technion, Tel Aviv University, and Ben Gurion University – are fully on board. This is a unique, adrenaline-intensive motorsport event that combines engineering theory and technological applications. We believe it will have a direct impact on the vehicle industry in Israel and encourage investors and local firms to develop vehicles and other relevant products.”

The opening event in August 2021 was attended by experts from the Ministry of Transportation, who advised the teams on adapting the car to comply with licensing requirements in Israel.

The student teams

The race will take place October 20-October 21 at the MotorCity – Motor Park Racing Circuit in Beersheba, Israel.

Formula Student is a series of international competitions in which university teams compete to design, manufacture, and race the best performing racecars.