A nanotech system invented in Israel for transporting anticancer drugs specifically in pediatric patients has been shown to slow tumor growth and prolong life expectancy in engineered mice by 42 percent. In most of the Western world, cancer is the primary cause of death in children over the age of one.
The new system meets an unmet need because existing chemotherapy treatments for adult cancer patients are not particularly effective for children due to differences in their physiology and in the way pediatric cancer cells grow and spread. In fact, conventional chemotherapy can cause severe damage to an ill child.
While highly targeted nanoparticle delivery systems show great promise in adult cancer patients, studies involving children have been limited. Prof. Alejandro Sosnik of the Technion-Israel Institute of Technology’s Department of Materials Science and Engineering, together with graduate student Alexandra Bukchin, used a mouse model to test their system for the selective transport of the chemotherapeutic drug Dasatinib via nanoscale packaging in young patients.
“The target audience is very physiologically fragmented and therefore less economically viable for pharmaceutical companies,” said Sosnik, who focuses on developing special treatments for children with cancer.
“The differences between children of different ages are great, and drug companies do not want to invest in research and development for such narrow age ranges. A child’s physiology is very different from that of an adult, so the tumor develops differently. The effects of drugs on the tumor are also not the same. In addition, clinical trials are rarely conducted on children for obvious reasons,” he said.
Dasatinib is currently administered in tablet form to inhibit tyrosine kinase, an enzyme that acts like a switch for activating and deactivating various cellular processes. Dasatinib can stop cancer growth but the current form of the drug is released in an untargeted way, affecting healthy cells as well as cancerous cells.
The nanotechnology delivery system developed by Sosnik and his team in Haifa is intended to transport the drug to cancer cells alone, thus maximizing its efficiency without harming healthy tissues. The transporter is made up of polymer micelles, nanostructures created by the self-assembly of polymers in water and considered to be an excellent method for transporting drugs, in part due to their tiny size (10 to 300 nanometers).
The major innovation in the Technion research is the addition of sugar to the nanoplatform. The cancer cell identifies the sugar and intakes the delivery system, releasing the drug inside the cell and inhibiting the enzyme activity.
In the initial lab experiment carried out by Sosnik’s group the efficacy of the new delivery system reduced the dosage of the drug needed to kill sarcoma cells – a cancerous tumor of muscles and bones which accounts for about 10% of tumors in children – in vitro by about 90%.
In collaboration with the research group of Dr. Angel Carcaboso from the Hospital Sant Joan de Deu-Barcelona, the efficacy of the delivery system was demonstrated in vivo using mice carrying tumor biopsies from pediatric patients. The delivery system significantly improved the accumulation of the drug into the tumor and prolonged the median lifespan of the engineered mice from 19 days (in the control group) to 27 days.
“I hope that the delivery system we have developed will improve the situation and serve to deliver a broad spectrum of anticancer drugs,” said Sosnik.
A paper published recently in the Journal of Controlled Release summarizes the three-year study that led to the first success in delivering Dasatinib with the help of these nanoparticles, and the first demonstration of the particles accumulating in the tumor in the patient’s tissue, in a model of pediatric cancer in experimental animals. The research was supported by Technion as well as grants from the European Commission.