Remote drug loading into liposomes

The development of liposome-based drugs was severely limited due to inefficient loading strategies. Herein, we developed a click reaction-mediated loading procedure by designing an enzyme-sensitive maleimide (MAL) tag for ferrying chemotherapeutics into preformed liposomes containing glutathione (GSH). Based on this strategy, various hydrophobic drugs could be encapsulated into liposomes within 5-30 min with encapsulation efficiency >95% and loading capacity of 10-30% (w/w). The entrapped cargo could be slowly released from the liposomes, followed by rapid enzyme-mediated conversion into active drugs to exert antitumor activity under physiological conditions. The resulting drug-loaded liposomes significantly prolonged the blood circulation of cargos and displayed more potent