Larch tree extract used to deliver drugs inside cancer cells
30 July 2010
By attaching a cancer drug to a polymer from the larch tree, researchers at the Technion-Israel Institute of Technology have developed a 'Trojan Horse' molecule that releases cancer-fighting drugs inside cancer cells, protecting healthy tissue.
The researchers created the molecule by attaching folic acid and an anticancer drug to a polysaccharide found in the Larch tree.
“We were looking for a natural polymer that would be highly soluble in water, and found it in a polysaccharide known as arabinogalactan, which is extracted from the Larix,” explained lead researcher Dr Yoav Livney, of the Technion Faculty of Biology and Food Engineering and the Technion Russell Berrie Nanotechnology Institute.
Certain cancerous cells produce between 10 to 100 times more folate receptors than healthy cells. These receptors bind to folic acid, which is required by cancer cells to grow and divide rapidly.
When the folic acid is bound to the receptor, the cell membrane folds inward, creating a bubble-like organelle called an endosome. These endosomes fuse with another type of organelle called a lysosome, which contains the cell's digestive enzymes. These enzymes digest peptides (a small fragment of protein), so in another clever step, the researchers attached the antitumour drug to the larch polysaccharide with a peptide that is specifically digested by the enzymes present in the lysosome.
As a result, the anticancer drug is released only in the lysosome, because there are no equivalent enzymes in the blood that can break down this specific peptide. So the healthy surrounding tissue is not affected.
The development is expected to be especially efficient against ovarian, kidney and uterine cancer, which are characterized by high production of folic acid receptors. In the future, this novel chemotherapeutic delivery system will be able to simultaneously deliver several anti-cancer drugs, whose tailor-made synergistic combination would lead to an optimal eradication of malignant cells of a specific cancer type, in individual cancer patients.
Also contributing to this research was Prof. Avi Domb, of the School of Pharmacy at Hebrew University of Jerusalem and Prof. Yehuda Assaraf of the Technion Faculty of Biology and head of the Fred Wiszkowski Cancer Research Lab.