Liposomes with Water as a pH‐Responsive Functionality for Targeting of Acidic Tumor and Infection Sites

A lipid named DCPA was synthesized under microwave‐assisted heating. DCPA possesses a pyridine betaine, hydrophilic group that can be complexed with water through hydrogen bonding (DCPA‐H(2)O). DCPA‐H(2)O liposomes became protonated relatively fast already at pH<6.8, due to the high HOMO binding energy of DCPA‐H(2)O. In murine models, DCPA‐H(2)O liposomes had longer blood circulation times than natural DPPC or cationic DCPM liposomes, while after tail‐vein injection DCPA‐H(2)O liposomes targeted faster to solid tumors and intra‐abdominal infectious biofilms. Therapeutic efficacy in a murine, infected wound‐healing model of tail‐vein injected ciprofloxacin‐loaded DCPA‐H(2)O liposomes exceeded the ones of clinically applied ciprofloxacin as well as of ciprofloxacin‐loaded DPPC or DCPM liposomes.