Human
glioblastoma tumors selectively express receptors for
interleukin 13 (IL-13). In a previous study, we showed that
liposomes, when conjugated with
IL-13, will deliver chemotherapeutics to a subcutaneous
glioma tumor model in mice much more effectively than conventional unconjugated
liposomes. Based on this observation, we developed an intracranial
brain tumor model in nude mice using human U87
glioma cells. Mice receiving weekly i.p.
injections of 15 mg/kg of
doxorubicin encapsulated in IL-13-conjugated
liposomes had a 5-fold reduction in the intracranial
tumor volume over 6 weeks and four of seven animals survived >200 days after
tumor implantation. In contrast, the animals receiving unconjugated
liposomes with the same
doxorubicin concentration did not survive beyond 35 days and there was no evidence of
tumor size reduction. The presence of
liposomes with
doxorubicin in the
tumor was shown by taking advantage of the selective expression of
IL-13 receptors on the
tumor cells and the endogenous fluorescence of
doxorubicin. There was no increase in the indices of toxicity in animals receiving the
doxorubicin-containing
liposomes. Finally, a model of the blood-brain barrier was used to show that the nanovesicles do not harm the endothelial cells yet maintain their toxicity to
astrocytoma cells. This approach is necessary to show the efficacy of this targeting platform for
tumors in which the blood-brain barrier is not compromised and as a potential use of the nanovesicle system as a surveillance mechanism to prevent recurrence. These data show that
IL-13 targeted nanovesicles are a viable option for the treatment of
brain tumors.