Nanoparticle Drug Delivery De-immunization Study
The human immune system can recognize and destroy foreign objects. In addition to bacteria and viruses, drug-delivering nanoparticles, implanted pacemakers, and artificial joints, which are also foreign, also trigger an immune response that causes drug failure, rejection, or inflammation. To this end, scientists at the University of Pennsylvania have developed a new method of attaching protein “passports” to these therapeutic devices so that they can pass through the body’s defense system.
The body will reject the invading foreign objects without discrimination, which is caused by the body’s natural immune system. This process involves a variety of cells, such as macrophages, which can detect, swallow and destroy invaders; serum proteins will stick to the target, causing macrophage attention, and once the macrophage determines that adhesive substance is foreign matter, it will swallow it, or signal other macrophages to surround it.
In order to avoid the natural immune response caused by nanoparticles, the early method is to coat them with a polymer “brush coat” that protrudes from the nanoparticles to prevent various serum proteins from sticking to its surface. But this can only be suspended for a while and cannot be finally resolved. Dennis Disco, a professor at the University of Pennsylvania, and the research team have another way: let macrophages believe that nanoparticles are “owners” and let them go.
As early as 2008, the Disco team discovered that there is a protein called CD47 on the human cell membrane that binds to the macrophage receptor SIRPa. Just like the patrolman checks people’s passes, the CD47 protein tells the macrophages that they are “owners, don’t eat me.” Later, other researchers cracked the connection structure between CD47 and SIRPa. With this information, the Disco team mapped the smallest amino acid sequence required to perform a CD47-like protein function and folded the “small peptide” as a solid “pass”. They chemically synthesized the small peptide, attached it to the anticancer drug delivery particles, and injected it into mice to test its efficacy. These mice have been genetically engineered to have the same SIRPĪ± receptor as humans. The researchers injected mice with two kinds of nanoparticles: one with a small peptide pass, the other without, and then measured how long it is identified by the mouse’s immune system. As a result, it was found that when the ratio of the initial injection of the two particles was 1:1, the number of particles having the small peptide was 4 times that of the without small peptide after 20 minutes to 30 minutes. This demonstrates that small peptides do inhibit the response of macrophages. In addition, the researchers also pointed out that these small peptides need further research before being put into practical use, reducing it to only a few amino acids. This step is critical. The simpler the passage molecule, the easier it is to synthesize. If it can be manufactured on a single machine and can be easily modified to accommodate a variety of implants and injections, it can be glued to a variety of drug delivery tools, or adhere to specialized antibodies to target cancer cells or other diseased tissues.