Photosensitizers for Skin Diseases Therapy
Novel Porphyrinic Photosensitizers for Photodynamic Therapy of Oncological and Non- Oncological Skin Diseases
Tech Area / Field
- BIO-IND/Industrial Biotechnology/Biotechnology
- MED-DID/Diagnostics & Devices/Medicine
- MED-DRG/Drug Discovery/Medicine
3 Approved without Funding
Vavilov State Optical Institute (GOI), Russia, St Petersburg
- St Petersburg State Medical University, Russia, St Petersburg\nElest Ltd
- Emred Oy, Finland, Helsinki\nUniversity Health Network / Princess Margaret Hospital, Canada, ON, Toronto
Project summaryIt is known that photodynamic therapy (PDT) is based on the damaging action of singlet oxygen within malignant and highly proliferating cells of any tissue. The main component of the PDT is a photosensitizer which is capable of accumulating selectively and being retained in cells for some time. Under light irradiation the photosensitizer molecules are excited into the metastable triplet state. The subsequent quenching of the photosensitizer triplet level by ground state molecular oxygen result in the formation of singlet oxygen, which being a strong cytotoxic agent, causes the death of malignant cells and thrombosis of tumor angiogenic vessels. Efficiency of the method is determined by a set of factors including the photosensitizer’s nature, laser power, selected absorbing region, depth of penetration of photosensitizer and of the light irradiation.
The possibility of injury of normal healty tissue in the course of the PDT (phototoxity) is an important factor. increasing the requirements on the photosensitizers.
In the project we propose to use porphyrins (coproporphyrin III and uroporphyrin), which are the natural metabolites of mammlian cells, as photosensitizers. Preliminary research works have shown that these pigments have high photoactivity, can be accumulated selectively in malignant tissue, can be excreted rapidly; they are non-toxic, penetrate well through the cutaneous barrier (stratum corneum) and are very effective in the case of neoplastic processes of different nature. These photosensitizers may be used in photodiagnostics of neoplastic and non-neoplastic diseases. So far the spectral and photophysical properties of the photosensitizers based on coproporphyrin III and uroporphyrin have not been explored enough. Optimal methods of light action of the photosensitizers mentioned above, ensuring the effective generation of singlet oxygen, are not determined. Besides, the process of penetration of the coproporphyrin III and uroporphyrin –based photosensitizers into different biological tissues has not been studied, including skin malignancies and benign tumors. This includes the optimal delivery vehicle of the photosensitizers, to ensure the biological accessibility., In the course of the project we are going to develop a liposome form of porphyrins.
Another constraint in the PDT method propagation is the commercial production of the photosensitizers. Provision for the photosensitizers synthesis available today are not scalable nor cost effective. For example, hematoporphyrin production of cattle blood is extremely cumbersome, quite dangerous and an unstable way in view of the raw products availability. The way of the photosensitizer production in chlorella cultivating cannot be recognized as a commercial one. Instability and hig variability of the end product is evident in this case.
Biotechnological method of the porphyrin production have very good prospects. Arthrobacter globiformis strains have a high rate of growth and stable output of porphyrins during the fermentation process. At that the coproporphyrin and uroporphyrin biosynthesis is realized with cultivating of one strain and using ion-exchange purification method. But, in spite of the prospects, the manufacturing technology of the porphyrin production, for example by assimilation of B12 vitamin production capacities, has not been developed. It is necessary to study a set of factors effecting the porphyrin ration in the culture and conditions for its purification.
The main goal of the project is to realize the photodynamic therapy method in medical practice using new photosensitizers coproporphyrin III and uroporphyrin in treatment of different skin diseases both oncological and non-oncological.
In the course of the project the following problems will be solved:
- Development of scientific grounds and technique of controlled biosynthesis of porphyrins and extraction of end products using ecologically clean and cost-effective methods.
- Study of spectral and photophysical properties of the coproporphyrin III and uroporphyrin-based photosensitizers.
- Experimental study of biological activity of the coproporphyrin III and uroporphyrin-based photosensitizers under different modes of light radiation.
- Preclinical trials of the coproporphyrin III and uroporphyrin-based photosensitizers drugs.
- Preparation of resulting documents on the project.
In the course of the project execution the participants will communicate with the foreign collaborators, discuss the results obtained at different stages of the project, compare the project results with the results obtained by the foreign collaborators in particular related to tasks 2 and 3 so that the experiments crucial for future commercialization of the new phototsensitizer are validated by a 2nd independent institution. This should also result in joint publications.
The project provides Russian weapons scientists an opportunity to redirect their talents to biomedical activities aimed at advancement of methods and means for treatment of oncological diseases. Peaceful applied research works will contribute to national and international biotechnological and healthcare problem solving.
The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.
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