Photodynamic therapy, which is mostly used in the treatment of skin cancers and known for its low side effects, cannot give the desired results when cancerous cells are located in deep areas where the rays cannot reach easily.
Bogazici University Chemistry Department faculty member Assoc. Dr. Sharon Çatak and his team embarked on a research that would eliminate this disadvantage of photodynamic therapy and double the ray-trapping capacity of the molecules responsible for ray-trapping. In the project led by Sharon Çatak, if antennas with two-photon absorbing properties are placed on molecules, how these molecules behave inside the cell will be calculated, and the results will guide the development of photodynamic therapy for the treatment of organ cancers located in deep tissues.
Bogazici University Chemistry Department faculty member Assoc. Dr. The project titled “Design of new photosensitizers for photodynamic therapy” under the direction of Sharon Çatak was entitled to be supported within the scope of TÜBİTAK 1001. In the project, which is planned to last for two years, Assoc. Dr. Çatak and one undergraduate, two graduate and one doctoral students are also involved as researchers.
A cancer treatment with minimal side effects
Photodynamic therapy (PDT), which is one of the approaches that does not require surgical intervention in cancer treatment, has very few side effects on the body compared to other cancer treatments. Assoc. Dr. Çatak explains how this treatment method works: “The drug given to the body in photodynamic therapy actually spreads throughout the body, but these drugs are drugs that are activated by radiation. For this reason, only the cancerous area to be treated is irradiated, and by activating the drugs in that area, it is possible to work with a target focus. Unactivated drugs are also excreted from the body. Therefore, the side effects of the treatment in the body are minimized. In addition, the cost is very low compared to other cancer treatments.”
The only disadvantage of photodynamic therapy is when cancerous cells are located in deep tissues where the rays cannot reach easily. Assoc. Dr. Çatak said, “The molecule that will effectively absorb the rays in the deep tissue is currently being investigated, therefore, treatment with PDT in deep tissue tumors has not been done much until now. However, in this project, we will try to overcome this limitation of PDT by suggesting drug molecules that can also be activated in deep tissues,” he says, adding that they aim to increase the effect of photodynamic therapy.
The light-trapping capacity of molecules will double
Stating that a drug molecule called PS (photosensitizer-photosensor) molecule is used in photodynamic therapy, Assoc. Dr. Sharon Çatak states that they aim to increase the effectiveness of the treatment with the antennas they will add to these molecules: “We will add antennas with two photon absorbing features to the FDA-approved PS molecule that we will work on. When two photon-absorbing antennas are added to these chlorine-derived molecules, it will be able to capture twice as many rays as normal. When the PS molecule receives the rays, it first becomes singlet excited, then, depending on the photophysical properties of the molecule, it changes from the singlet excited state to the triplet excited state. On the other hand, by encountering the oxygen in the body environment, which is at triplet level by nature, the triplet excited PS molecule transfers energy to the oxygen and makes the oxygen reactive. In other words, the task of the molecule here is to absorb the beam and transfer the energy provided by that beam to oxygen. In short, it is actually oxygen, not the PS molecule, that does the job of lysing cells; but this molecule is responsible for reactive oxygen.”
According to Çatak, photodynamic therapy can be more effective for cancer cells located in deep tissues, depending on the ability of PS molecules to absorb more rays: “We want to add antennas that can absorb two photons on the PS molecule so that it can absorb energy in deep tissues. Because, even if the injected PS molecule goes to the deep tissue, it cannot absorb effectively at this wavelength and therefore the FDT activity of this molecule is not possible here. However, the high wavelength light (red light) used in the treatment can penetrate deep tissue. With this approach, when we add two photon absorbing antennas to the molecule, we will double the number of photons absorbed. We'll also have a chance to test how these molecules move through body tissue under laboratory conditions and how drugs interact with the cell membrane."
A guide for experimental chemists
Emphasizing that the project is purely a theoretical molecular modeling study and that it will proceed with simulations in the computer environment, Assoc. Dr. Sharon Çatak explains the advantages of the project's outputs as follows: “There are already laboratories where the molecules we mentioned are synthesized, we will investigate how they behave in the cell through modeling. The advantage of these studies that go into computational chemistry comes from being able to find the photophysical properties of molecules in great detail. We give experimental chemists predictions about which molecule they can modify and how, so that they can synthesize molecules based on what we find by calculating instead of trial and error over and over, and we speed up the process very much.”
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