Biomimetic phosphorylcholine strategy to improve the hemocompatibility of pH-responsive micelles containing tertiary...

pH-responsive nanocarriers such as polymeric micelles that self-assemble from amphiphilic copolymers containing amino groups have been limited by their significant effects on the blood and thus compromise of their hemocompatibility due to the amino group-induced positive charges. Here we report a biomimetic phosphorylcholine strategy to improve the hemocompatibility of the pH-responsive micelles with positive charges. Amphiphilic copolymers containing different number of tertiary amino groups were synthesized in five steps through ring opening polymerization, azide reaction, thio-bromo "Click" chemistry, and atom transfer radical polymerization to self-assemble biomimetic phosphorylcholine micelles with pH-responsiveness, which shown no significant effects on red blood cells, coagulation, and platelet activation. Moreover, albumin adsorption on the micelles was significantly lower than that of polycaprolactone-methoxypolyethylene glycol (PCL-mPEG) control, and in terms of immune cells, the micelles showed controllable phagocytosis that dependent on the number of tertiary amino groups, in which the one containing four tertiary amino groups in its corresponding copolymer remains had a lower phagocytosis by whole blood leukocyte than that of PCL-mPEG. Based on these results, the hemocompatibility related mechanism of the micelles was discussed and proposed. Our findings demonstrated that this biomimetic phosphorylcholine is a promising strategy to improve the hemocompatibility of the positively charged nanocarriers.