Abstract
Zwitterionic phosphocholine (PC) liposomes are widely used in drug delivery because of their high biocompatibility and long blood circulation time. We herein report that by flipping the direction of the PC dipole, the resulting choline phosphate (CPe) liposomes have an even longer circulation time, as confirmed at both cellular and animal-model levels. Even when 33% cholesterol was included in the lipid formulation with a poly(ethylene glycol) layer, the CPe liposome still had a longer blood circulation time. Isothermal titration calorimetry indicates a lack of protein adsorption or PC membrane attachment for the CPe liposomes. This is different from the previously reported adhesion of CP polymers to PC lipid membranes, which may be attributed to the different ways of displaying the CP headgroup. With a longer blood circulation time, the CPe liposomes accumulated in tumors more easily than PC liposomes, which is likely due to the enhanced permeation and retention effect and tumor cell uptake. This study provides key insights into zwitterionic biointerfaces for biomedical, analytical, and materials applications.