Nanocapsules against sepsis

Researchers from Moscow and Pushchino have developed an effective method for obtaining and targeted delivery of an anti-inflammatory drug based on human heat shock protein

The press release is published on the website of the Russian Academy of Sciences

Despite many years of research aimed at studying treatment approaches, sepsis or "blood poisoning" remains the main cause of death, both in our country and abroad. In the USA and in European countries, 500,000 patients develop sepsis annually, with the number of confirmed cases increasing by 1.5% per year. The joint work of a group of researchers from the Institute of Cell Biophysics of the Russian Academy of Sciences, the Institute of Molecular Biology of the Russian Academy of Sciences, the Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences and the Pushchinsky Research Center Hospital is dedicated to preventing the development of this severe pathology.

The leading cause of death in gram–negative sepsis, a systemic inflammatory reaction, is endotoxin shock. The toxic effects of gram-negative bacteria are caused by thermally stable lipopolysaccharides called endotoxins. In the initial stage of endotoxin shock, these toxic substances interact with blood phagocytes and cause an inflammatory response, which is characterized by an increase in the level of cytokines in the bloodstream, as well as the formation of reactive oxygen species by cells. Recent clinical studies aimed at analyzing the reduction of mortality of patients from sepsis depending on the therapy used have shown almost no progress in the treatment of this disease and the ineffectiveness of available antibiotics in the treatment of this most dangerous disease.

Of great importance in inflammatory processes, as well as in the body of a healthy person, is the main stress highly conserved heat shock protein BTSH70. An increase in the concentration of this protein in the blood occurs not only with heat stress, but also with the action of various factors: ischemia, trauma, high physical activity, ultraviolet radiation, bacterial infection, inflammation. BTSH70 is a molecular chaperone: it is necessary to maintain cellular functions and helps newly synthesized proteins in the cell to fold properly.

Employees of the V. A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences have developed an innovative method for obtaining highly purified BTSH70. In their experiments, they found that the introduction of BTSH70 before the introduction of endotoxins significantly reduces the mortality of model animals and normalizes the main blood parameters. The joint work of the staff of the IMB RAS and the Institute of Cell Biophysics of the Russian Academy of Sciences demonstrated that human BTSH70 reduces the production of reactive oxygen species, tumor necrosis factor α of blood phagocytes and macrophages caused by the action of bacterial endotoxins. Scientists have suggested that BTSH70 can be used as an agent that protects cells and the body as a whole from the action of bacterial pathogens. However, for effective treatment of any disease, targeted drug delivery is necessary. Polyelectrolyte microcapsules are one of the ways to deliver proteins and other biologically active compounds to cells along with liposomes. The most promising is the use of biodegradable capsules, the shell of which gradually disintegrates in cells due to the action of intracellular enzymes. It is this method of delivery and its modifications that has been proposed and tested for various pharmacological preparations by scientists from ITEB RAS.

"Encapsulated protein has a number of advantages over non–encapsulated protein," says Lyudmila Ivanovna Shabarchina, senior researcher at the Laboratory of Cytotechnology of the ITEB RAS, "this is the possibility of targeted delivery of biologically active substances, and prolonged exit from microcapsules; as well as protection of protein from destruction and sorption in body fluids during delivery to cells. In this regard, microcapsules consisting of biodegradable components, such as polypeptides and polysaccharides, have great prospects for use both at the cellular and organizational levels."

The work carried out by the joint efforts of Pushchinsky and Moscow scientists demonstrates that polyelectrolyte microcapsules are easily absorbed by blood phagocytes. At the same time, the biodegradable microcapsules themselves do not have a toxic effect on innate immunity cells, practically having no effect on ROS production and neutrophil apoptosis. "In this work, we have shown the possibility of delivering BTSH70 to innate immunity cells using polyelectrolyte microcapsules," comments Maxim Grigoryevich Vinokurov, head of the Apoptosis Regulation Laboratory at the Institute of Cell Biophysics, on the study. "We have found that with this method of delivery, encapsulated BTSH70 inhibits neutrophil apoptosis more effectively than non-encapsulated protein. In addition, it was found that encapsulated BTSH70 reduces the production of tumor necrosis factor induced by LPS to values comparable to the protective effect of the non-encapsulated protein."

Nanocapsules in monocytes. Figure from the article Yurinskaya et al. Encapsulated Hsp70 decreases endotoxin-induced production of ROS and TNFa in human phagocytes, published in the journal Cell Stress and Chaperones – VM.

The results obtained by scientists allow us to consider the possibility of using microcapsules consisting of biodegradable polyelectrolytes for effective delivery of the BTSH70 protein to the cells of the innate immunity system. The developed method of delivering a protective stress protein to cells can also be used for other therapeutic drugs of a protein nature.

Portal "Eternal youth" http://vechnayamolodost.ru  27.04.2017