11.01.2017 change 11.01.2017

Researchers at the University of Silesia improve phototherapy to fight cancer

Researchers at the University of Silesia are working on improving photodynamic therapy used in the fight against cancer as an alternative or supplement to radiotherapy or chemotherapy. In December, Polish researchers obtained Polish patent for a mixture improving its effectiveness.

Dr. Robert Musioł reminded that photodynamic therapy consists in introducing photosensitive substances into the patient that accumulate in diseased cells and, under the influence of light, generate deadly oxygen radicals, killing unwanted cells. This allows for a very precise removal of tumours from the body.

"Unfortunately, the methods used until now are not perfect. There are problems with the low effectiveness of therapy, because the light penetrates tissue relatively shallowly - only to a few millimetres. The biggest problem is, therefore, that when using the currently approved photosensitizers we are forced to move only on the surface layer of the tissue. This makes it impossible to completely remove large tumours, something always remains somewhere deeper" - told PAP scientist whose every day activities include research and search for potential new drugs.

One of the chances to improve the effectiveness of phototherapy may be the development of drugs that would improve the effectiveness of the photosensitizer, and at the same time would "enter" deeper into the cells than light. "Then, in addition to attacking cancer with light from the outside, even if we do not completely remove the tumour by irradiating the spot - there is a chance that the other, +internal+ medicine will complement this action" - explained Musioł.

The invention patented by researchers from the University of Silesia is a mixture of thiosemicarbazone 2-carbaldehyde-3-aminopyridine with a photosensitizer. It is an iron chelator, causing the "capture" of the micro-nutrient from the cells.

"Most currently used derivatives of aminolevulinic acid use of natural mechanisms occurring in the cell and related to iron metabolism in the process of accumulation of the photosensitizer. At the end of this process light-sensitive protoporphyrin IX is produced that is converted into a molecule of heme by binding iron. Because heme does not display the properties of a photosensitizer - the idea is to reduce the metal concentration" - he explained.

He added that reducing the amount of iron in the cancer cell allows to more effectively create photosensitive protoporphyrin. Scientists during their research also found that some iron binders further improve the effectiveness of therapy through other mechanisms, involving the production of free oxygen radicals. "This way, a reinforced, cascade therapeutic effect is achieved" - explained Musioł.

Thus obtained synergy effect allows to reduce the dosage, which, in turn, eliminates the occurrence of side effects. Studies conducted at the University of Silesia show that 95 percent effectiveness of the mixture on the cells of the colon tumour HCT116 can be achieved with eight times lower dose of the chelator than with monotherapy.

"For now, these are experiments conducted in vitro, a further step may be +in vivo+, or work in an animal model, and only then possibly implementation. Unfortunately, it all comes down to financial capabilities" - he added.

According to Musioł, photodynamic therapy is already used in Poland. "And it turns out that in some, sometimes very complicated cases, as in the case of brain tumours, but also tumours of intestines and lungs, it works" - he noted.

It is also used, for example, in diagnosis or surgery. "Photosensitizer, which is given in preparation for treatment, accumulates in the diseased tissue, and if you illuminate it, it begins to glow differently than the surrounding, healthy tissue. Hence, combined therapies are used. The surgeon sees what he should remove, and at the same time the tumours too small for the resection will be destroyed using photosensitizer and light" - he explained.

According to Musioł, photodynamic therapy is cheaper than radio or chemotherapy. It is also less harmful to the patient. "Using radiotherapy we often also irradiate the rest of the patient\'s body, which is associated with a lot of side effects. Here we typically use a laser diode, which is relatively cheap and it can irradiate a small portion of the body" - he said.

Therefore, in this scenario - the scientist said - the drawback of relatively shallow penetration of light into the tissue becomes an advantage. "Cancers which are not scattered through the body, they are not metastatic tumours but only uniform ones or birthmarks on the skin, can be relatively easily spot- exposed. This approach works particularly well for the treatment of skin lesions, or mucous membranes" - he added.

The authors of the recently patented invention are employees of the Faculty of Mathematics, Physics and Chemistry, University of Silesia: Dr. Anna Mrozek-Wilczkiewicz, Prof. Alicja Ratuszna, Dr. Robert Musioł and Prof. Jarosław Polański. In the near future, scientists plan further studies other cell lines and preparations for work on animals as part of a National Science Centre grant carried out by Dr. Mrozek-Wilczkiewicz.

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