Minimal "Self" Peptides That Inhibit Phagocytic Clearance and Enhance Delivery of Nanoparticles

TLDR

Phagocytes clear foreign particles but must avoid clearing self cells, a process marked by CD47 signaling through the phagocyte receptor CD172a. The authors computationally designed minimal CD47‑derived peptides, synthesized them, and conjugated them to virus‑sized particles for intravenous injection into mice expressing a CD172a variant compatible with human CD47. Self peptides delay macrophage clearance of nanoparticles, prolong circulation, enhance tumor dye and drug delivery, bind CD172a with near‑optimal affinity, potently inhibit cytoskeleton‑mediated uptake, and demonstrate the utility of human Self peptides for drug delivery and imaging.

Abstract

Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. The membrane protein CD47 is reportedly a "marker of self" in mice that impedes phagocytosis of self by signaling through the phagocyte receptor CD172a. Minimal "Self" peptides were computationally designed from human CD47 and then synthesized and attached to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47. Self peptides delay macrophage-mediated clearance of nanoparticles, which promotes persistent circulation that enhances dye and drug delivery to tumors. Self-peptide affinity for CD172a is near the optimum measured for human CD172a variants, and Self peptide also potently inhibits nanoparticle uptake mediated by the contractile cytoskeleton. The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.