Every nanoparticle injected into blood is instantly coated by serum proteins — the protein corona. If that corona is rich in opsonins (IgG, complement fragment C3b), macrophages read it as an "eat me" flag and engulf the particle via Fc-receptor / complement-receptor phagocytosis. Real cells, including healthy tissue, additionally display CD47 on their surface, a "marker of self" that binds the macrophage receptor SIRPα and actively suppresses engulfment — a "don't eat me" signal. Nanoparticles engineered with CD47-mimetic peptides or fragments hijack this same checkpoint.
This 2D top-down view of the bloodstream compartment gives every circulating particle a simplified phagocytic score built from both signals, then rolls the dice on contact with the macrophage's capture zone (dashed ring):
corona(t) = Ops_max · (1 − e^(−t/τ)), Ops_max = opsonin · (1 − 0.85·PEG)
score = corona(t) − k_CD47 · CD47
P(eat) = 1 / (1 + e^(−(score − θ)/s)) ← logistic checkpoint decision
P(eaten in dt) = P(eat) · dt / τ_decision (rolled while particle ⊂ macrophage capture zone)
- Opsonin level sets how strongly "hot", complement/antibody-rich serum tags bare nanoparticle surface.
- PEG stealth coating sterically blocks protein adsorption sites, capping how much corona can ever form (τ is the corona build-up time constant).
- CD47 density subtracts directly from the phagocytic score through the SIRPα checkpoint — enough of it can override even a fully opsonized surface, exactly as it does for platelets and red blood cells evading the spleen.
- Particle colour blends blue (stealthy) → red (opsonized/flagged) as its live score rises; an engulfed particle shrinks into the macrophage and a fresh one respawns at the arena rim, keeping the circulating population steady so the readouts settle into a steady-state clearance rate.
- The mini strip chart tracks the phagocytosis rate over the last 20 s; the histogram shows where the live circulating population currently sits relative to the decision threshold θ (dashed line) — drag the arena to pan, scroll/pinch to zoom.
This is the same design trade-off behind clinical PEGylated liposomes (Doxil) and CD47-blockade/mimicry research in oncology nanomedicine: too little stealth and the reticuloendothelial system clears the dose in minutes; too much and active targeting ligands can't find their receptor either.