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Research Articles: Therapeutics, Targets, and Development

Interleukin-13 receptor–targeted nanovesicles are a potential therapy for glioblastoma multiforme

¹ Department of Neurosurgery, Milton S. Hershey Medical Center, Penn State University, Hershey, Pennsylvania; and ² Department of Nuclear Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

Requests for reprints: James R. Connor, Department of Neurosurgery (H110), G.M. Leader Family Laboratory for Alzheimer's Disease Research, Milton S. Hershey Medical Center, Penn State University, 500 University Drive, Hershey, PA 17033-0850. Phone: 717-531-4541; Fax: 717-531-0091. E-mail: jconnor{at}psu.edu

Abstract

The difficulties associated with treatment of malignant brain tumors are well documented. For example, local infiltration of high-grade astrocytomas prevents the complete resection of all malignant cells. It is, therefore, critical to develop delivery systems for chemotherapeutic agents that ablate individual cancer cells without causing diffuse damage to surrounding brain tissue. Here, we describe sterically stable human interleukin-13 (IL-13)–conjugated liposomes, which efficiently bind to the brain cancer cells that overexpress the IL-13 receptor 2 protein. The conjugated liposomes bind to glioblastoma multiforme tissue specimens but not to normal cortex. Conjugating the liposomes with human IL-13 allows for specific binding to glioma cells and uptake of the liposomes via endocytosis. Delivering doxorubicin to glioma cells by IL-13–conjugated liposomes results in enhanced cytotoxicity and increased accumulation and retention of drug in the glioma cells compared with delivery of free drug. The therapeutic potential and targeting efficacy of the IL-13–conjugated liposomes carrying doxorubicin was tested in vivo using a s.c. glioma tumor mouse model. Animals receiving i.p. injections of IL-13–conjugated liposomes carrying doxorubicin for 7 weeks had a mean tumor volume of 37 mm³ compared with a mean volume of 192 mm³ in animals injected with nontargeted liposomes. These results strongly suggest that IL-13–conjugated liposomes carrying cytotoxic agents are a feasible approach for creating a nanovesicle drug delivery system for brain tumor therapy. [Mol Cancer Ther 2006;5(12):3162–9]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 8/10/06; revised 9/30/06; accepted 10/27/06.