Encapsulation of doxorubicin in magnesium acetate liposomes as a pH-sensitive drug carrier for tumor therapy

The pH-sensitive drug release is an appealing strategy to enhance the therapy efficacy of anti-tumor liposomal drugs. In this study, we constructed the pH-sensitive magnesium-doxorubicin (Mg-DOX) liposomes by remote-loading of DOX into MgAc₂ gradient liposomes. The prepared 100 nm Mg-DOX liposomes (Mg-DOX-Lip100) and folate receptor targeting Mg-DOX liposomes (FA-Mg-DOX-Lip100) were stable at physiological pH condition but gradually released DOX at acidic media. The FA-Mg-DOX-Lip100 exhibited much higher uptake by tumor cells and cytotoxicity <i>in vitro</i> than the Mg-DOX-Lip100. The Mg-DOX liposomes also showed stability in circulation in mice and delayed the growth of orthotopic EO771 tumor in C57BL/6 mice similar to Doxil-like liposomes at DOX dose of 5 mg/kg body weight every 4 days for 4 times, without observable morphologic change of the dissected organs at experiment endpoints. Thus, the pH-sensitive Mg-DOX liposomes have been successfully constructed and approved to be a potential antitumor delivery system to treat acidic tumors.