In Vivo Antitumor Activity of Folate Receptor-targeted Liposomal Daunorubicin in a Murine Leukemia Model

Background: Folate receptor (FR) is selectively amplified among human tumors, including in 70% of myeloid leukemias. FR-targeted liposomal delivery is an attractive strategy for enhancing the therapeutic efficacy of anticancer agents against FR(+) tumors. In this study, FR-targeted liposomal daunoru...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Anticancer research 2005-01, Vol.25 (1A), p.343-346
Hauptverfasser: PAN, Xing Q, LEE, Robert J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Background: Folate receptor (FR) is selectively amplified among human tumors, including in 70% of myeloid leukemias. FR-targeted liposomal delivery is an attractive strategy for enhancing the therapeutic efficacy of anticancer agents against FR(+) tumors. In this study, FR-targeted liposomal daunorubicin was evaluated in an FR+ L1210JF murine ascites tumor model for therapeutic efficacy in vivo. Materials and Methods: FR-targeted liposomal daunorubicin (F-L-DNR) and non-targeted liposomal daunorubicin (L-DNR) were prepared by polycarbonate membrane extrusion followed by remote loading of DNR. FR-targeted liposomal uptake by L1210JF cells was characterized in vitro using fluorescent liposomes entrapping calcein. For in vivo therapeutic study, B6D2F1 mice on a folate-free diet were intraperitoneally implanted with FR (+) L1210JF cells and treated with 4 intraperitoneal injections of 10 mg/kg liposomal DNR at 1, 5, 9 and 13 days following tumor cell inoculation. Animal survival was then monitored daily. Results: L1210JF cells showed ~ 10 3 times greater uptake for FR-targeted liposomal calcein compared to the non-targeted control. Uptake of the targeted liposomes could be blocked by 1 mM folic acid. In the therapeutic study, mice treated with F-L-DNR showed significantly greater tumor inhibition and 40.7% greater increase in life-span compared to those that received identical doses of L-DNR. Meanwhile, free DNR given at the same dose failed to prolong the survival of the treated mice. Conclusion: F-L-DNR can effectively target FR(+) leukemia cells in vivo. Further preclinical evaluation is warranted to determine its potential application in leukemia therapy.
ISSN:0250-7005
1791-7530