Fig. 1: Dendrimer characteristics and the role of dendrimer end-terminal functionality in complement activation.

a Structural representation of G2–G5 dendrimers with magnified views of the highlighted end-terminal region (dashed triangles). At physiological pH the end-terminal primary amines and carboxylic acids are predominantly protonated and deprotonated, respectively. b Typical structure of a G4 PAMAM dendrimer with a precisely core positioned sulforhodamine B. c Selected properties of G2–G5 dendrimers. *The values for radius of gyration were adopted from a previous small-angle X-ray scattering study²⁶ d Pyrrolidone- and carboxy-Tris-terminated dendrimers do not trigger complement activation in human plasma (plasma code, M26; a healthy individual Caucasian, male, 26 years old) as determined through measurements of sC5b-9. Complement activation is compared at an equivalent number of dendrimer terminal groups (101 × 10¹⁷ terminal groups per mL of plasma). e The effect of different generations (G2–G5) of amine-terminated dendrimers on generation of fluid-phase sC5b-9 in M26 plasma. The best coefficient of correlation (R² = 0.965) is computationally defined by the equation y = 422.15e^0.0106x. f The effect of G2 dendrimer concentration on sC5b-9 formation in M26 plasma. The best coefficient of correlation (R² = 0.955) is computationally defined by a quadratic polynomial fit (y = −0.0319x² + 0.2006x + 366.92). In e and f, mean background sC5b-9 levels were 367 ± 7.2 µgmL⁻¹ and 361 ± 7.3 µgmL⁻¹, respectively. In panel d, bars represent mean ± s.d. of three separate experiments and each dot indicates the mean of three technical replicates. In e and f, each point represents the mean ± s.d. of three separate experiments, and each experiment was done in triplicate samples. In d, e and f, p values (unpaired, two-sided) are compared with the respective background (control) incubation. Source data are available in Source data file.