| Title | Improved therapeutic activity of folate-targeted liposomal doxorubicin in folate receptor-expressing tumor models. | | Author(s) | Gabizon A, Tzemach D, Gorin J, Mak L, Amitay Y, Shmeeda H, Zalipsky S | | Institution | Experimental Oncology Laboratory, Shaare Zedek Medical Center, 11 Shmuel Bayit Street, 7th Floor, P.O. Box 3235, Jerusalem, 91031, Israel, alberto.gabizon@gmail.com. | | Source | Cancer Chemother Pharmacol 2009 Sep 25. | | Abstract | PURPOSE: The folate receptor (FR) is overexpressed in a broad spectrum of malignant tumors and represents an attractive target for selective delivery of anti-cancer agents to FR-expressing tumors. Targeting liposomes to the FR has been proposed as a way to enhance the effects of liposome-based chemotherapy.
METHODS: Folate-polyethylene glycol-distearoyl-phosphatidyl-ethanolamine conjugate was inserted into pegylated liposomal doxorubicin (PLD). The therapeutic activity of folate-targeted (FT-PLD) and non-targeted (PLD) pegylated liposomal doxorubicin was tested in two human tumor models (KB, KB-V) and in one mouse ascitic tumor model (FR-expressing J6456) by the i.v. systemic route in all models, and by the i.p. intracavitary route in the ascitic tumor model only.
RESULTS: Consistent with previous studies, PLD was clearly superior to free doxorubicin in all tumor models. When targeted and non-targeted liposome formulations were compared, FT-PLD was more effective than PLD in the KB and KB-V xenograft models, and in the J6456 intra-cavitary therapy model. The therapeutic effect was dose-dependent in the KB model and schedule-dependent in the J6456 intra-cavitary therapy model. In some experiments, toxic deaths aggravated by folate-depleted diet were a major confounding factor. In a non-FR expressing J6456 model, FT-PLD was as active as PLD indicating that its activity is not limited to FR-expressing tumors.
CONCLUSION: Folate-targeting confers a significant albeit modest therapeutic improvement to PLD in FR-expressing tumor models, which appears particularly valuable in intracavitary therapy. The potential clinical added value of this approach has yet to be determined. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19779718 |
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