Molecule Helps Nanoparticles Sneak Past the Immune System

Taking a cue from nature, researchers have designed nanoparticles that can avoid being destroyed by the immune system by convincing immune cells that the particles are part of the body. The advance represents a fundamentally new way to address a major obstacle facing nanoparticle-based drug delivery.

Nanoparticles are attractive for use in targeted drug delivery and imaging, but the immune system’s innate response to foreign particles is an impediment to the advancement of many nanoparticle-based drugs and imaging techniques.

Now, in a paper published today in Science, researchers describe nanoparticles designed not to hide from immune cells, but to engage them in order to secure passage through the body.

To accomplish this, the researchers attached a molecule derived from the human body’s own “marker of self,” a protein called CD47, which is present in nearly every mammalian cell membrane. CD47 binds to a specific regulatory protein, signaling to the immune cell that its cell is part of the body and should be spared. Other molecules may perform the same or similar functions, says Dennis Discher, a professor of biophysical engineering at the University of Pennsylvania, who led the research, but so far CD47 is the only one known to transmit the “don’t eat me” message to a type of immune cell called a macrophage.

Discher’s group computationally designed the smallest sequence of amino acids—the “minimal peptide”—that would retain this function in humans, and attached it to conventional nanoparticles. They then demonstrated that fluorescent nanoparticles equipped with the peptide and aimed at tumors in mice allowed for enhanced imaging of those tumors compared to controls. “This really works in vivo,” says Discher. “We were able to show just in this initial application that we can image tumors with particles that are utterly useless without this peptide.”

The strategy represents a useful new way of looking at the interaction of nanoparticles with the immune system, and “will make a major impact on the field” of nanomedicine, says Samir Mitragotri, a professor of chemical engineering at the University of California, Santa Barbara. Mitragotri, who was not involved in the research, highlights the fact that the paper’s authors identified the peptide that can stand in for CD47 as a molecular passport. Peptides, or short sequences of amino acids, are easier to handle and work with than full proteins, he says.

This particular peptide can be relatively easily made, says Discher, and can be modified so it attaches to a variety of different materials.