title: Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels.
abstract: Recently, cationic liposomes have been shown to preferentially target the angiogenic endothelium of tumors. It was the aim of our study to investigate the influence of liposomal surface charge on the uptake and kinetics of liposomes into solid tumors and tumor vasculature. Experiments were performed in the amelanotic hamster melanoma A-Mel-3 growing in the dorsal skinfold chamber preparation of male Syrian golden hamsters. Fluorescently labeled liposomes with different surface charge were prepared. Accumulation of i.v. injected liposomes was assessed by quantitative intravital fluorescence microscopy of tumor and surrounding host tissue. The histological distribution of liposomes was analyzed by double-fluorescence microscopy 20 min after application of fluorescently labeled lectin as a vascular marker. After i.v. application of anionic and neutral liposomes, we observed an almost homogeneous distribution of liposome-induced fluorescence throughout the chamber preparation without specific targeting to tumor tissue. In contrast, cationic liposomes exhibited a significantly enhanced accumulation in tumor tissue and tumor vasculature up to 3-fold compared to surrounding tissue (p<0.05). The histological distribution of neutral and anionic liposomes revealed extravasation 20 min after i.v. injection, while cationic liposomes displayed a highly selective accumulation on the vascular endothelium. In conclusion, cationic liposomes exhibited a preferential uptake in angiogenic tumor vessels and therefore may provide an efficient tool for the selective delivery of diagnostic or therapeutic agents to angiogenic blood vessels of solid tumors. On the other hand, anionic and neutral liposomes may be used as carriers of drugs to the extravascular compartment of tumors due to their extravasation.
authors.affiliation: Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Germany.
authors.forename: Senat
authors.initials: S
authors.lastname: Krasnici
authors.forename: Alexander
authors.initials: A
authors.lastname: Werner
authors.forename: Martin E
authors.initials: ME
authors.lastname: Eichhorn
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmitt-Sody
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Pahernik
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sauer
authors.forename: Brita
authors.initials: B
authors.lastname: Schulze
authors.forename: Michael
authors.initials: M
authors.lastname: Teifel
authors.forename: Uwe
authors.initials: U
authors.lastname: Michaelis
authors.forename: Kurt
authors.initials: K
authors.lastname: Naujoks
authors.forename: Marc
authors.initials: M
authors.lastname: Dellian
mesh_terms: D000818:Animals; D002412:Cations; D006224:Cricetinae; D015194:Diffusion Chambers, Culture; D016503:Drug Delivery Systems / Q000379:methods; D004730:Endothelium, Vascular / Q000378:metabolism; D007275:Injections, Intravenous; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply*; D008647:Mesocricetus; D009389:Neovascularization, Pathologic; D013499:Surface Properties; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D002412:Cations; D008081:Liposomes