Drug-delivery nanoparticles naturally trigger this response, so researchers' earlier attempts to circumvent it involved coating the particles with polymer "brushes." These brushes stick out from the nanoparticle and attempt to physically block various blood serum proteins from sticking to its surface.
However, these brushes only slow down the macrophage-signaling proteins, so Discher and colleagues tried a different approach: Convincing the macrophages that the nanoparticles were part of the body and shouldn't be cleared.
In 2008, Discher's group showed that the human protein CD47, found on almost all mammalian cell membranes, binds to a macrophage receptor known as SIRPa in humans. Like a patrolling border guard inspecting a passport, if a macrophage's SIRPa binds to a cell's CD47, it tells the macrophage that the cell isn't an invader and should be allowed to proceed on.
"There may be other molecules that help quell the macrophage response," Discher said. "But human CD47 is clearly one that says, 'Don't eat me'."
Since the publication of that study, other researchers determined the combined structure of CD47 and SIRPa together. Using this information, Discher's group was able to computationally design the smallest sequence of amino acids that would act like CD47. This "minimal peptide" would have to fold and fit well enough into the receptor of SIRPa to serve as a valid passport.
After chemically synthesizing this minimal peptide, Discher's team attached it to conventional nanoparticles that could be used in a variety of experiments.
"Now, anyone can make the peptide and put it on whatever they want," Rodriguez said
The research team's experiments used a mouse model to demonstrate better imaging of tumors and as well as improved efficacy of an anti-cancer drug-delivery particle.
As this minimal peptide might one day be attached to a wide range of drug-delivery vehicle
University of Pennsylvania