Angiogenesis is the formation of new blood vessels upon tumor development and growth in the body, each tumor when it forms in the body needs its own supply of nutrition and oxygen; it is a complex, multistep process that involves expression of proangiogenic growth factors which trigger recruitment of inflammatory cells, remodeling of the extracellular matrix, and endothelial cell processes such as migration and proliferation. All these factors lead to the sprouting of new vessels from preexisting vascular networks. Ofra and her team are trying to develop drugs that can block blood supply to the tumors. What they basically do is that they apply bioengineering principles to the cancer and drug delivery research and investigate the tumor’s microenvironmet; how the body supports its growth.
“The research we do is multidisciplinary; I have a very diverse team including experts in many fields; there are chemists, physicists, biologists, pharmacists and physicians” says Ofra.
Benny’s laboratory is divided into three main areas of research: the first is drug discovery, the development of new anti-cancer drugs, with a basic understanding of drugs that can inhibit the formation of blood vessels for tumors.
The second innovative and interesting area is the development of rational design, which implements the knowledge of engineering and technological fields. “Proper planning of drug carriers can increase their selectivity to cancer cells and intensify the entry of drugs into cancerous tumors” Ofra adds.
Ofra and her team are trying to develop drugs that can block blood supply to the tumors. Angiogenesis, the formation of new blood vessels upon tumor development and growth in the body is provide tumors with their own supply of nutrition and oxygen; Benny’s group designing drug vehicles that can “sense” the angiogenic area and accumulate there.
What they basically do is that they apply bioengineering principles to the cancer and drug delivery research and investigate the tumor ‘s microenvironmet; how the body supports its growth. “ The research we do is multidisciplinary; I have a very diverse team including experts in many fields; there are chemists, physicists, biologists, pharmacists and physicians” says Ofra.
The first two aspects led to the third and significant research field, which is building of the human model, to help predict in advance whether a particular drug will work or not; utilizing chips and micro devices serving as an innovative tool for diagnostics.
“We do the “organ on chips” and more specifically tumor on chip. We take biopsies from patients, we process them in a certain way that we can grow them as a 3-D entity and in a fluid manner on the chip itself, then we screen different types of drugs to finally give a decision which of them can work; we can even predict if the body may develop a resistance to this specific drug. This actually enables us to accurately predict whether the patient needs to start chemotherapy or not” Ofra explains.
Cancer on a chip
For the nanomedicine and drug delivery research field; mostly for cancer therapy, they’re currently focusing on the delivery of these drugs into the target organ. In the case of cancer, the drugs in general are very non-selective. “We’re working on making drugs more selective by targeting them more efficiently. In that aspect we design different types of nanoparticles with precisely tunable properties. We’re addressing the basic research questions of how properties of drug and the drug delivery systems affect their interactions with cancer cells versus normal cells. We try to optimize our system and tune its properties to end up having an increased selectivity even before adding the drug inside; I believe that we’ll be able to get better drug selectivity even individually for patients depending on each specific case” Dr. Benny says.
She adds “An interesting thing we’re doing in collaboration with Prof. Magdassi, is the 3-D printed drugs; we design and print drug tablets in which we control the release of drug by varying the geometry of the tablets.”
When asked about challenges regarding her research Ofra says: “The medicine field in general is going through revolutions. We need to be able to make better and more precise predictions in order to decide which drug and drug delivery system is more efficient and suitibale for each patient depending on his condition; we need to analyze a lot of data with the right and even smarter tools. It's that kind of research which takes a lot of time and requires continuous and generous funding. One of the challenges especially related to this field is that sometimes the technology we use in our research is much more advanced than the technology used on the market. Drug development and commercialization needs to be approved in order to eventually enter the market; we have to meet the specifications and take into consideration the regulations; this is restricting our design and engineering ideas”.
“Our nanocenter is a very essential place for us that serves our research a lot” Ofra says. “We fabricate our chips in the clean room in the unit of nanofabrication (UNF). We also heavily use the characterization techniques in the unit of nanocharacterization (UNC), such as the scanning and the transmission electron microscopes (SEM and TEM), the atomic force microscope (AFM), the X-ray diffraction (XRD) and others, in order to characterize our drug particles and evaluate its physical and chemical properties such as size, shape, composition, texture, flexibility and morphology, which all have dramatic effects on the way they interact with cells in general and with cancer cells in particular. This of course is crucial for increasing the efficacy of cancer drugs. However, it would be fantastic if they have a wet TEM for characterizing biological samples. We rely heavily on the equipment as well as on the technical staff operating it. The equipment is very complex and we need the staff to operate it in order to conduct our research. The staff at the Center is well experienced and they play a vital and intregal part in the process and analysis of our research” concludes Ofra.