(193f) ‘Active Stealth' Signaling with a Synthetic 'self' Peptide

Foreign particles and cells are rapidly cleared from the body by professional phagocytes that incessantly encounter and recognize ‘self’ cells.  The membrane protein CD47 is reportedly a ‘Marker of Self’ in mouse that impedes phagocytosis of self cells, with signaling through the highly polymorphic receptor CD172a on phagocytes.  Here, minimal ‘Self’ peptides were computationally designed from CD47^human, synthesized with anchoring groups, and attached to virus-size nanoparticles for intravenous injection into NOD.SCID (NSG) mice that express a unique CD172a^NSG (or SIRPA) compatible with CD47^human.  ‘Self’ peptides delay splenic macrophage clearance of particles with an exponential advantage in persistent circulation, which we use to enhance near-infrared imaging of human tumor xenografts by >10-fold.  The affinity of CD47^human for CD172a^NSG proves weak but within the broad range (0.1 ~ 5 microMolar) measured for ten constructed variants of CD172a^human; several versions of ‘Self’ peptide are likewise shown to bind and potently inhibit nanoparticle uptake by an unexpected cytoskeletal mechanism.  The reductionist approach reveals the importance and utility as well as some limits of a human ‘Self’ peptide.