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
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.