In vitro evaluation and biodistribution of HER2-targeted liposomes loaded with an 125I-labelled DNA-intercalator
2011 (English)In: Journal of drug targeting (Print), ISSN 1061-186X, Vol. 19, no 9, 846-855 p.Article in journal (Refereed) Published
Background: Increasing attention is currently focussed on the issue of finding strategies for the delivery of Auger-electron emitting radionuclides into tumour cell nuclei. Nuclear localisation is a prerequisite for these radionuclides, since their radiotoxic properties are functional only in close vicinity to DNA.
Purpose: In this study we investigated tumour-cell uptake and cell killing ability in vitro, as well as in vivo biodistribution of an 125I-labelled anthracycline derivative administered by means of HER2-targeted liposomes.
Methods: Anthracycline derivative Comp1 was radiolabelled with Auger-emitting 125I 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 125I-Comp1 delivered via targeting and non-targeting liposomes were analysed in cultured HER2-overexpressing SKOV3 and SKBR3 cells. Cell-killing efficacy was evaluated in SKOV3 cells and biodistribution for up to 48 hours was studied after intra-peritoneal injection in tumour-bearing female Balb/c nu/nu mice.
Results: 125I-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 125I-Comp1 accumulated in tumours when distributed using HER2-targeted liposomes and that this effect was absent when using non-targeting liposomes.
Conclusion: The HER2-targeted liposomes possess the properties needed to bring about tumour-specific delivery and therapeutic effect of 125I-Comp1.
Place, publisher, year, edition, pages
2011. Vol. 19, no 9, 846-855 p.
IdentifiersURN: urn:nbn:se:uu:diva-147028DOI: 10.3109/1061186X.2011.589436ISI: 000295889800013OAI: oai:DiVA.org:uu-147028DiVA: diva2:399741