Collaboration between the Organic Chemistry Department and the Biophysics Department at the Lobachevsky University with the Research Institute of Macroheterocyclic Compounds has resulted in the development of a new, highly selective anti-tumor photodynamic therapeutic agents.
A team of researchers from Lobachevsky University (Nizhny Novgorod, Russia) headed by Professor Alexei Fedorov, Ph.D, Chair of the Organic Chemistry Department, is developing a new generation of targeted anti-cancer drugs for photodynamic therapy.
Since every case cancer and every cancer patient is different and unique, there are multiple treatment strategies. While some of these approaches are based on a single agent approach, some others may involve different, combination therapies.
According to Alexei Fedorov, one approach includes photodynamic therapy. “In this method, a special substance, a photosensitizer that is injected into the bloodstream or applied to the affected area of the skin, is used to destroy tumors. When this molecule is activated by light, a number of chain processes are initiated that result in the death of tumor cells,” Fedorov explained.
However, currently existing photosensitizer agents may have a number of serious advantages. One of the observed problems involved the relatively low selectivity of accumulation in tumor tissue. Following administered, these agents are distributed almost evenly between healthy tissues and those affected by tumors. To offer a therapeutic benefit, this balance needs to shift towards predominant accumulation in tumors. Current efforts of researchers in many countries are trying to achieve this goal.
To address this problem, Fedorov and his team conjugated the therapeutic properties of classical photosensitizers based on natural chlorophyll with highly selective molecules based on targeted drugs. The idea is simple enough: to synthesize two separate molecules with different but important properties, and then combine them to produce one molecule with a full set of properties. This approach has significant improved the pharmacological properties of the novel, targeted, agent.
In collaboration with the help of the scientists from the Research Institute of Chemistry of Macroheterocyclic Compounds (Ivanovo), the starting material was isolated to create the photosensitizer part of the conjugate from the Arthrospira blue-green algae. The targeting compounds were obtained from the Lobachevsky University.
Biological tests conducted on cell and animal models at the Lobachevsky University Biophysics Department have shown that the synthesized molecules accumulate more efficiently and faster than molecules containing only the photosensitizer. The results of were published in the January 2018 edition of the European Journal of Medicinal Chemistry.
However, this was just the first stage of the project. After obtaining the initial positive results, a vast field opens for optimizing the structure of the molecule in order to reduce the toxicity of drugs and to increase their selective effect on tumor tissues.
Currently, work is under way to create the next generation of photosensitizer conjugates that will surpass their predecessors in most aspects. Preclinical trials are planned for the most effective new compounds.