29 Jan '19
Russian biologists and biophysicists a few years ago developed minuscule particles to act as capsules for target delivery of drugs and useful substances to blood cells. The discovery has been used to create a new medicine to fight sepsis.
“An encapsulated protein has a number of advantages, including target delivery of bioactive substances, a longer-than-usual release from microcapsules, and the protection of the protein against disintegration as it moves to cells. That’s why microcapsules that consist of biodegradable components have wider applications,” said Lyudmila Shabarchina of the Institute of Theoretical and Experimental Biophysics (ITEB) in Pushchino outside Moscow.
Over the past decade Russian and international researchers have come up with a few dozen types of hollow nanoparticles that cause no immune response and can infiltrate all but just a very few cells in the human body. These have been “remodeled” to become containers for the delivery of drugs that either decompose fast in blood flow or the stomach, or are too toxic for other organs and tissues. All this enables physicians to either reduce doses of medicines or make them more convenient and safer for the treatment of most deadly diseases, such as cancer.
Ms. Shabarchina and her team at ITEB, in partnership with colleagues from the Moscow-based Institute of Molecular Biology, have found ways of bringing into immune cells a special protein that protects the cells from toxin overloads and resultant death, thus adding sepsis to the list of diseases to be treated with target delivery technology.
Sepsis is a life-threatening condition that arises when the body’s response to infection causes injury to its own tissues and organs. Immune cells die en masse under the attack of toxins contained in microbes that have filtered through vessel walls and into blood flow. Once in blood and immune cells, the intruders trigger inflammation, fueling it with chemically aggressive molecules. That destabilizes the entire vascular and immune systems, and many organs end up getting no access to blood flow at all. About 50% of such cases result in patients’ imminent death.
The human or animal body takes steps to prevent such an outcome by generating a range of anti-inflammatory proteins that help cells keep on in stressful conditions. One of the key such molecules is Hsp70, a human heat shock protein that guards other proteins against tangling and damage as the cell’s “protein factories” assemble them.
Playing with the protein reportedly led the Russian team to the conclusion that inserting Hsp70 into the body of a mouse or other animal inhibits sepsis development, a discovery that caused the scientists to believe a synthetic Hsp70 version could be used as a remedy for sepsis.
It took skill, time and painstaking work to create such a remedy, as the protein must be delivered to the right cells and prevented from decomposing as it travels through the body. To solve the problem, the ITEB biophysicists developed nanoparticles of ordinary chalk and organic polymers which gradually dissolve when acted upon by enzymes in cells.
The researchers filled the nanoparticles with Hsp70 solution and experimented to see what happens when the particles are placed in a culture of immune cells that fight microbes. As a result, the concentration of aggressive molecules inside the cells that had absorbed the nanoparticles was reduced by 50%, which prevented the cells from mass destruction and the development of a most dangerous inflammatory response in the test-tube they lived in.
The scientists think similar nanoparticles could be used for the delivery of other proteins and drugs that tend to decompose inside the body or are unstable by nature. In addition, the Hsp70 containing nanoparticles themselves could also help in the fight against cancers and brain diseases that stem from mass cell decease caused by disarrays in internal protein assembly.