Fig. 5. Mechanisms of C3 deposition inhibition by SCR-2-3-4:

A) a general (simplified) scheme of C3 deposition on pathogen surface. The deposition starts with generation of C3b through lectin pathway (LP) or classical pathway (CP), or with spontaneous addition of C3/C3b through various mechanisms.[59] Following the initial deposition step, there is an amplification step via AP. CP activation can be inhibited by C1 inhibitor, and LP and CP activation can be inhibited by EGTA/Mg2⁺; B) SPIO NWs, Feraheme, LipoDox and Onivyde were incubated in plasma in the presence or absence of SCR-2-3-4 (4.1 µM), EGTA/Mg²⁺, or 125 µg/mL C1 inhibitor as described in Methods. C1INH did not block C3 deposition, whereas EGTA/Mg²⁺ decreased deposition by 50%. The data demonstrate that all the particles activate complement via the AP and LP, but not the CP. SCR-2-3-4 appears to inhibit C3 deposition via both AP and LP. Individual data points of 3 technical replicates for each donor are shown.