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

 

Hydrogen On the Way

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Hydrogen On the Way
Researchers in the Schulich Faculty of Chemistry at the Technion have developed a new system for producing hydrogen from water with a low energy investment and using available and inexpensive materials

Water electrolysis is an easy way to produce hydrogen gas. While hydrogen is considered a clean and renewable fuel, efficient electrolysis today requires high electric potential, high pH and in most cases, catalysts based on ruthenium and other expensive metals. Due to the inherent promise of hydrogen, many research groups are striving to develop electrolysis technologies that will make it possible to produce hydrogen fuel at a low electric potential, at a pH between 7-9 and with catalysts based on available and inexpensive metals such as copper, manganese, and cobalt.

Professor Galia Maayan

The Journal of the American Chemical Society  recently reported on a unique solution for this issue developed at the Technion – Israel Institute of Technology. It is the fastest system of its kind reported so far that operates with available metal (copper) catalysts. The research was led by Professor Galia Maayan, head of the Biomimetic Chemistry Laboratory in the Schulich Faculty of Chemistry, and doctoral student Guilin Ruan.

The Technion researchers designed and developed a homogeneous electrolysis system, or in other words, a system in which the catalyst is soluble in water, so that all components of the system are in the same medium. The innovative and original system is based on (1) copper ions; (2) a peptide-like oligomer (small molecule) that binds the copper and maintains its stability; and (3) a compound called borate whose function is to maintain the pH in a limited range. The main discovery in this study is the unique mechanism that the researchers discovered and demonstrated: the borate compound helps stabilize the metallic center and participates in the process so that it helps catalyze it.

Doctoral student Guilin Ruan

In previous studies, the research group demonstrated the efficacy of using peptide-like oligomers to stabilize metal ions exposed to oxygen – exposure that may oxidize them in the absence of the oligomer and break down the catalyst. Now, the researchers are reporting on the success in creating a very efficient and fast electrolysis system. The stable system oxidizes the water into hydrogen and oxygen under the same desired conditions: low electric potential, pH close to 9 and inexpensive catalysts. According to Prof. Maayan, the system was inspired by enzymes (biological catalysts) that use the protein’s peptide chain to stabilize the metallic center and by natural energetic processes such as photosynthesis, which are driven by units that use solar energy to transport electrons and protons.

Copper complex, consisting of two molecules of a peptide-like oligomer that binds two copper ions, reacts under electrolysis conditions with a molecule of the borate compound; the product of the reaction is the catalyst that allows the water to oxidize and create oxygen and hydrogen efficiently and quickly.

The research was supported by the Israel Science Foundation (ISF) and the Nancy and Stephen Grand Technion Energy Program.

Click here for the paper in The Journal of the American Chemical Society

Distinguished Prof. wins Prestigious Award

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Dist. Prof. Nitzan Zohar

Distinguished Professor Yitzhak Apeloig of the Schulich Faculty of Chemistry has been awarded the 2021 Schrödinger Medal of the World Association of Theoretical and Computational Chemists (WATOC). Past recipients of this honour include four Chemistry Nobel Prize winners and many of the pioneers of computational quantum chemistry.

The prestigious medal is awarded each year to a single scientist whose contribution to theoretical and computational chemistry is particularly outstanding. Professor Apeloig’s selection was based on his seminal contributions to the chemistry of organosilicon compounds and to organic chemistry, and for the impressive combination of experimentation, computations, and theory in his research.

Professor Apeloig joined the Technion faculty in 1976 and served as President of the university from 2001 to 2009. He pioneered the use of computational tools based on quantum theory to predict molecular characteristics and molecular reactions, as well as organosilicon chemistry. He has received a plethora of important awards, including the Taub Award for academic excellence, the Distinguished Teacher Award from the Technion, the Humboldt Prize, the award of the Japan Society for the Promotion of Science (JSPS), the gold medal of the Israel Chemical Society, the Wacker Silicone Award, and the ACS Kipping Award in Silicon Chemistry. He is an honorary member of the American Academy of Arts and Sciences and a member of the European Academy of Sciences, holds an honorary doctorate of science from the Berlin Institute of Technology, has been awarded the Order of Merit of the President of the Federal Republic of Germany, and is an honorary citizen of Haifa, Israel.

The World Association of Theoretical and Computational Chemists (WATOC) aims to promote the field of theoretical and computational chemistry and to advance the interactions between scientists working in this field worldwide. Its most recent congress was attended by 1,500 scientists from all around the world.

The Schrödinger Medal is named after the Austrian physicist Erwin Schrödinger, one of the fathers of quantum mechanics and a Nobel Prize laureate who developed a wave equation named after him – the Schrödinger equation.  Some WATOC members work on developing mathematical methods and computer programs to solve the equation. Others, including Prof. Apeloig, apply these methods to study and predict the characteristics and reactions of various compounds. Prof. Apeloig was one of the first experimental chemists in the world to realise the potential of computational methods and applied them in his research already in the 1970s.

Today, many chemistry studies in the academy and in the industry (such as the development of new compounds, new medicines, etc.) are performed using computational methods, most commonly in a collaborative effort between experimenting and calculating research groups. One of the unique features of Prof. Apeloig’s research is that the experimental and computational research are usually performed by the same student, who acquires knowledge in both disciplines, an important factor in his/her scientific development.