In vitroevaluation and biodistribution of HER2-targeted liposomes loaded with an125I-labelled DNA-intercalator

Increasing attention is currently focussed on the issue of finding strategies for the delivery of Auger-electron-emitting radionuclides into tumor cell nuclei.In this study, we investigated tumor-cell uptake and cell-killing ability in vitro as well as in vivo biodistribution of an (125)I-labelled anthracycline derivative administered by means of HER2-targeted liposomes.Anthracycline derivative Comp1 was radiolabelled with Auger-emitting (125)I and encapsulated in liposomes (DSPC:Chol:DSPE-PEG) using pH-gradient loading. Single-chain fragment F5 was anchored to the liposomes as targeting device for HER2. Uptake and specificity of (125)I-Comp1 delivered via targeting and non-targeting liposomes were analysed in cultured HER2-overexpressing cells. Cell-killing efficacy was evaluated in SKOV3 cells and biodistribution for up to 48 h was studied after intraperitoneal injection in tumor-bearing female BALB/c nu/nu mice.(125)I-Comp1 was specifically taken up by the cultured cells when administered by means of HER2-targeted liposomes and a clear dose-effect correlation in survival of cells was seen with increasing specific activity. The biodistribution studies revealed that (125)I-Comp1 accumulated in tumors when distributed using HER2-targeted liposomes and that this effect was absent when using non-targeting liposomes.The HER2-targeted liposomes possess the properties needed to bring about tumor-specific delivery and therapeutic effect of (125)I-Comp1.