Stable Incorporation of a Lipophilic Daunorubicin Prodrug into Apolipoprotein E-Exposing Liposomes Induces Uptake of Prodrug via Low-Density Lipoprotein Receptor in Vivo

Many tumors express elevated levels of low-density lipoprotein (LDL) receptors. Therefore, native LDL and synthetic LDL-like particles have been proposed as carriers for antineoplastic drugs. We demonstrated earlier that small apolipoprotein E (apoE)-exposing liposomes were specifically recognized by the LDL receptor. In this study, we incorporated a lipophilic deriv-ative of daunorubicin (LAD) into the apoE liposomes. Up to 11 molecules of LAD could be incorporated per particle without significantly changing the size, lipid composition, and ability to bind apoE of the liposomes. The biological fate of the prodrug was largely determined by its carrier (70 % of the initially incor-porated LAD was still associated to the liposomes after 4 h of circulation in mice). Compared with free daunorubicin, the cir-culation half-life of the liposome-associated prodrug was sub