<div>Zwitterionic polycarboxybetaines (PCBs) have gained attention as alternative stealth polymers whose</div><div>liposomal formulation and protein conjugates were reported not to elicit anti-polymer antibodies. Here, we</div><div>studied the blood retention and antigenicity of liposomes modified with PCBs focusing on their chemical</div><div>structures and doses. We compared PCBs with either 1 or 3 (PCB1 or PCB3) spacer carbons between the</div><div>carboxylate and ammonium groups. PCB3-modified liposomes had a short blood retention, whereas PCB1-</div><div>modified liposomes demonstrated extended blood retention that was somewhat superior to PEGylated liposome.</div><div>This confirmed the excellent non-fouling nature of PCB1 reported previously. Interestingly, PCB1-liposome as</div><div>well as PCB3-liposome elicited specific IgMs toward each PCB. The dose-dependent production of specific</div><div>IgMs to PCB-liposomes was similar to that of PEGylated liposome, i.e., high doses of PCB-liposomes reduced</div><div>the production of specific IgMs, termed immunological tolerance. These results indicate the importance of</div><div>investigating the effect of dose to clarify the existence of antigenicity of stealth polymers</div>