The body’s innate immune system is its first line of defense against invaders. A disease-causing bacterium or a piece of wood from a splinter are treated the same: cellular agents of the immune system identify these objects as foreign and try to destroy them.

Macrophages — literally, “big eaters” — are a main part of this response. These cells find and engulf invaders, or form a wall around the foreign object. Unfortunately, macrophages also eat helpful foreigners, including nanoparticles that deliver drugs or help image tumors.

Along with members of his lab, Dennis Discher, professor of chemical and biomolecular engineering in the School of Engineering and Applied Science at the Univ. of Pennsylvania, has developed a “passport” that could be attached to therapeutic particles and devices, tricking macrophages into leaving them alone.

The immune system’s macrophages act like border guards, binding to objects as they pass through the bloodstream and inspecting them to see if they belong there or not. One way a body’s own cells identify themselves is via a protein on their membranes.

“We simulated and synthesized the simplest functional version of that membrane protein, and then stuck this ‘minimal peptide’ on the exterior of some plastic nanoparticles,” Discher says. “We then tested whether they would fool the immune system into thinking they were part of the body.”

Giving therapeutic nanoparticles more time before they are eaten by macrophages could be a major boon for treatments. Some nanoparticles might need to get through the macrophage-heavy spleen and liver to find their targets, but shouldn’t stay in the body indefinitely. Other combinations might be appropriate for more permanent devices, such as pacemaker leads.   

While more research is necessary before such applications become a reality, the relative simplicity of this passport molecule makes it a more attractive component for future therapeutics. “It can be made cleanly in a machine,” Discher says, “and easily modified during synthesis in order to attach to all sorts of implanted and injected things, with the goal of fooling the body into accepting these things as ‘self.’”