Nanoparticles disguised from the immune system
In order to be as effective as possible, the drugs must get directly inside the tumor or the diseased cells. Despite the successes in the development of nanoparticles-carriers capable of delivering drugs to their destination, all of them face a serious obstacle on the way to the goal – the patient's immune system. The main enemy of carrier nanoparticles are macrophages - immune cells, one of the main functions of which is the absorption and destruction of foreign objects entering the body through a mechanism known as phagocytosis.
Researchers at the University of Pennsylvania, working under the leadership of Dennis Discher, have proposed a new way of producing nanoparticles carrying therapeutic agents disguised as the body's own cells. With the help of computer modeling, they developed and synthesized a small fragment of CD47 membrane protein consisting of 21 amino acids, which interacts with CD172a receptors on macrophage membranes as an "own" signal in response to a request from the control system during air travel.
After that, the authors conducted an experiment on mice that were simultaneously injected with the same dose of two modifications of commercially available polystyrene nanobusins. One of the modifications was coated with a synthesized oligopeptide and labeled with a fluorescent dye. Nanobusins of the second modification were marked only with a fluorescent dye different from the one used in the manufacture of the first modification.
An analysis carried out 30 minutes after administration showed that the blood of animals contained four times more nanobusins of the first type than of the second. This indicates that the peptide synthesized by the authors really prevents the absorption of nanoparticles by macrophages.
By binding to the macrophage receptor (gray), the synthetic peptide (yellow) prevents the neutralization of therapeutic nanoparticles by the immune system.Further experiments on mice with tumors showed that nanobusins labeled with peptide and fluorescent dye accumulate in tumors.
Such selective accumulation is due to the fact that nanoparticles exit through large pores of the walls of blood vessels penetrating the tumor and get stuck in structureless tumor tissue.
When an animal model of nanobusins loaded with molecules of the antitumor drug paclitaxel was introduced, a decrease in the size of malignant tumors was observed, not inferior to the results of using a standard paclitaxel carrier – chemophore. At the same time, no side effects of unpacked chemophore were observed in animals.
The developers of the "stealth coating" hope that the efficiency of this system will be further enhanced through the use of specially modeled nanoparticles.
Article by Rodriguez P.L. et al. Minimal "Self" peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles is published in the journal Science.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru
01.03.2013