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

Wang, DY (Wang, Da-Yuan) 1, 2, 3Yang, G (Yang, Guang) 1, 2, 3van der Mei, HC (van Der Mei, Henny C.) 2, 3Ren, YJ (Ren, Yijin) 4, 5Busscher, HJ (Busscher, Henk J.) 2, 3Shi, LQ (Shi, Linqi) 1

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2021

DOI 10.1002/anie.202106329

Abstract

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-H2O). DCPA-H2O liposomes became protonated relatively fast already at pH<6.8, due to the high HOMO binding energy of DCPA-H2O. In murine models, DCPA-H2O liposomes had longer blood circulation times than natural DPPC or cationic DCPM liposomes, while after tail-vein injection DCPA-H2O 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-H2O liposomes exceeded the ones of clinically applied ciprofloxacin as well as of ciprofloxacin-loaded DPPC or DCPM liposomes.