Science: synthetic peptides can fool the immune system

According to the latest research results published in science No.21, scientists have successfully synthesized a peptide molecule, which can "trick" the immune molecules to release the binding compound after binding with nanoparticles, so that it can move smoothly in human body The "self peptide" designed by computer can be used to design better tumor drugs, ensure that pacemakers will not be rejected, and also can be used to improve medical imaging technology "This is the first peptide molecule that can combine with any substance to weaken the immune system," said Dennis Discher, a professor of Biophysical Engineering at the University of Pennsylvania Professor Dennis Discher is also a co-author of the study According to Joseph de Simone, a chemical engineer at the University of North Carolina in the United States, "this strongly proves the feasibility of the concept of biological escape strategy." Macrophages recognize, phagocytize, and remove foreign invaders, whether they are microbes entering through wounds or nanoparticles loaded with drugs to treat specific diseases In the past, researchers have tried to wrap the polymer "brush" around the nanoparticles to organize the blood protein to adhere to the nanoparticles, so that they can not warn macrophages of foreign invasion However, this technology not only delays the signaling of macrophage signaling protein, but also hinders the absorption of drugs by disease cells With this in mind, Discher and colleagues are trying to find a new way to trick macrophages into treating nanoparticles as part of the body In their previous studies, they have found a membrane protein called CD47 that binds to human macrophages and signals the immune system to "own people." As a result, particles that bind to this protein are not attacked by the immune system After studying the binding structure between CD47 and SIRP α, a synthetic peptide with similar binding structure was designed This is the key to open the innate immune reconciliation After obtaining the 21 amino acid "autopeptide" by chemical synthesis, the researchers combined it with nano beads and injected it into genetically engineered mice, which contain human like SIRP α It was found that the beads with "self peptide" remained in the blood longer than the beads without "self peptide": after 30 minutes of injection, the number of beads with synthetic peptide was 4 times of that without synthetic peptide These results show that the synthesized molecules can reduce the ratio of macrophages to clear microspheres In another experiment, the researchers fluorescently stained the beads with and without synthetic peptides and then injected them into mice with lung cancer It was found that the beads combined with synthetic peptide could accumulate in tumor through macrophage filled liver and spleen This provides a clearer signal for medical imaging In fact, the signal intensity provided by the bead binding synthetic peptide in tumor is consistent with that of the bead binding human CD47 protein Finally, in order to test whether the biological strategy can be successfully used to bind targets, the researchers added anticancer drugs to the "self beads" coated with antibodies against cancer cells As expected, these "self beads" coated with antibodies are better than those not bound with synthetic peptides in reducing tumor size This confirms that when the antibody attracts the attention of macrophages, the autopeptide inhibits the macrophage's response by signaling "don't eat me" These results confirm that the synthetic peptide can prolong the retention time of therapeutic nanoparticles in vivo, which improves the delivery effect of drugs In addition, the relative simplicity of this peptide makes it easy to be synthesized, which is conducive to its use in various applications.