Multistage pH-responsive liposomes for mitochondrial-targeted anticancer drug delivery.

Zwitterionic oligopeptide liposomes (HHG2C(18)-L) containing a smart lipid (1,5-dioctadecyl-L-glutamyl 2-histidyl-hexahydrobenzoic acid, HHG2C(18)) are developed to overcome the barriers faced by anticancer drugs on the route from the site of injection into the body to the final antitumor target within transport steps with multiple physiological and biological barriers. HHG2C(18)-L show the multistage pH-responsive to the tumor cell (the mitochondria in this case). Their multistage pH response leads to more effective entry of the tumor cell, improved escape from the endolysosomes, and accumulation at the mitochondria (see picture).