Protein ‘Passport’ That Help Nanoparticles Get Past Immune System

Paul A. Janmey and Dennis E. Discher

Mary Leonard, Biomedical Art & Design, University of Pennsylvania This MRSEC Seed co-supported work shows a colloid +/- peptide signaling to the cytoskeleton, impacting cytoskeletal organization and membrane curvature near the colloid's surface.

Mary Leonard, Biomedical Art & Design, University of Pennsylvania
This MRSEC Seed co-supported work shows a colloid +/- peptide signaling to the cytoskeleton, impacting cytoskeletal organization and membrane curvature near the colloid’s surface.

What’s the Problem?   Macrophages are part of the innate immune system and will try to eat anything they don’t recognize as being part of the body — they’re like border patrol guards, checking everybody’s passports. If you’re a red blood cell, you have the right passport and get waved on. But if you’re a piece of dirt or a bacterium, you don’t have the right passport, and Macrophages get you. The problem is that there are some things we actually want to be in body, like drug-delivery particles, that get eaten by these macrophages, too.

What’s the Solution?  Other approaches involve trying to physically block macrophages from checking the nanoparticle’s passport — trying to sneak past the guards with ‘polymer brushes’. What we’re doing is different — we’re forging passports. We took a human protein that’s on the exterior of all human cells that tells macrophages ‘don’t eat me’, and we simulated and synthesized the simplest functional version of it.
We stuck this “minimal peptide” on the exterior of some plastic nanoparticles and then tested whether they would fool the immune system into thinking they were part of the body.

How do we know it worked?  We first made a competition of it in mice: we dyed nanoparticles with peptide one color and used a second color for nanoparticles without peptide, and then we mixed 1:1 and injected. Just 20 minutes later, there was up to four times as many particles with the peptide.  We also put some antibodies on the nanoparticles, because you would have something like that on there if you wanted them to target a particular tissue.  These antibodies also serve the purpose of attracting the macrophage’s attention, so we knew they are checking the nanoparticles passports. As a final proof, we showed particles with peptide do a better job of delivering dyes and drugs to cancer sites.

[ press release ] [ article in Science ]