Interleukin-13 receptor-targeted nanovesicles are a potential therapy for glioblastoma multiforme.
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 alpha2 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.
Madhankumar
A B
AB
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, USA.
Slagle-Webb
Becky
B
Mintz
Akiva
A
Sheehan
Jonas M
JM
Connor
James R
JR
D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D018793:Interleukin-13 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D053660:Receptors, Interleukin-13 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D018793:Interleukin-13; D008081:Liposomes; D053660:Receptors, Interleukin-13; D004317:Doxorubicin