With chlorophyll against cancer
A promising method for fighting cancer, the so-called photodynamic therapy, has now been significantly improved. Instead of the usual substances, Israeli scientists use chlorophyll derivatives, which can be used much more effectively. Photodynamic therapy, or PDT, in which cell-destroying substances are activated by light, has attracted enormous interest in medical circles in recent years. However, PDT currently has some limitations: it is only effective on relatively flat and superficial tumors, such as certain types of skin and bladder cancer. The light needed to activate the substances does not penetrate deep enough into human tissue. In addition, patients undergoing PDT must avoid the sun for weeks after treatment because their skin is overly sensitive to strong light.
The new drugs derived from chlorophyll could now help to overcome these problems and make it possible to use PDT against massive and deeper tumours. In addition, patients would probably only need to avoid the sun for a day or two after therapy.
The new active ingredients were developed by Avigdor Scherz from the Plant Sciences Department and Yoram Salomon from the Biological Regulation Department of the Weizmann Institute of Science and have so far been tested in tissue cultures and in mice. Relatively large malignant melanoma tumors could be destroyed in the mice. In tissue culture, the drugs were also effective against other types of cancer cells, including breast and colon cancer. The Dutch company Steba Beheer NV is now developing it for clinical use worldwide."If successful, our 'green' PDT could become an effective new weapon in the fight against cancer in the future," says Prof. Scherz.
PDT uses drugs that are only toxic when exposed to light. First, the drug is injected into the bloodstream or tumor and allowed to accumulate in the abnormal cells. Then the tumor is exposed to light in a controlled manner. The result is that the drug is activated and destroys the tumor cells.
"The major advantage of this treatment compared to conventional chemotherapy is that the effect of the drug is confined to the illuminated tumor site, minimizing damage to he althy tissue and significantly reducing side effects," says Prof Solomon.
Previous active ingredients used in PDT are based on heme, the red pigment derived from hemoglobin. They are activated only by visible light, which has limited penetration into tissue. In addition, they only function in the presence of oxygen, which is scarce within many solid tumors. Therefore, they can only destroy thin and flat tumors or tumors in early stages of development.
By contrast, the Weizmann Institute's materials-derived from the green chlorophyll pigments that make green plants and photosynthetic bacteria such effective light collectors-can be used against larger solid tumors. In addition to visible light, they also absorb mid-infrared light, which can penetrate much deeper into body tissues. In addition, they also work under hypoxic conditions, i.e. when the oxygen content in the tissues is below normal. These properties make them superior to current photosensitive drugs.
Another advantage of the new chlorophyll derivatives is that they are eliminated from the patient's body much faster after treatment than the previous drugs. This property is due to the fact that the new materials have been modified to be water soluble. This accelerates their removal from the tissue. Therefore, patients can endure sunlight shortly after the treatment without fear that the photosensitive materials will damage their skin. The aqueous solubility also has the advantage of making the materials easier to administer to patients.
In order to transport the active substances exactly to the desired location, the scientists bind them to antibodies or other transport molecules.
In examining the new drugs, it turned out that they first destroy the blood vessels that supply the tumor. Without these blood vessels, the tumor cannot develop. Then the materials destroy the tumor itself.
The scientists are also investigating the potential use of the new materials as antimicrobial drugs. A new study showing that the chlorophyll derivatives are effective in killing disease-causing bacteria was published in December 1997 in Photochemistry and Photobiology. Given the growing problems of bacterial resistance to antibodies, this application of the new chlorophyll derivatives could be particularly important.
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