DDEL-13TARGETED INTERLEUKIN-13-LIPOSOMES-MAGNIVEST-DOXORUBICIN FOR DETECTION AND TREATMENT OF GLIOMA IN EARLY STAGE

Abstract

Malignant glioma in central nervous system (CNS) is a challenge to detect/treat due to the blood-brain barrier (BBB) that prohibits most chemicals like anti-cancer agents to penetrate. Furthermore, to detect brain cancer, magnetic resonance image (MRI) contrast agent such as Magnevist (Gd/DTPA) is limited to the cases where the BBB is significantly compromised by the cancer because Gd-DTPA itself is not able to cross the BBB. As a result, the cancer boundary presented by Gd-DTPA-enhanced MRI reflects only the extent where BBB is compromised instead of all the cancer-infiltrated regions. For the malignant glioma in early stage when it is smaller than 2 mm, which is even none detectable by Gd-DTPA-enhanced MRI because the BBB is intact when tumor is less than 2 mm. It is critical to develop a delivery system that carries targeted MRI contrast agent with drug alongside, which could penetrate brain tissue, detect and treat glioma in early stage concomitantly. Previous work demonstrated: 1) IL-13Rα2 was over-expressed in glioma, 2) IL-13-liposomes-doxrubinsine inhibited an intracranial glioma growth and 3) IL-13-liposomes-Gd/DTPA as a MRI contrast agent enhanced and detected infiltrating glioma. Based on these findings we hypothesized that IL-13-liposome encapsulating Gd-DTPA and doxorubicin (Dox) will be a theranostic agent for detection and treatment of gliomas. To test our hypothesis, glioma U251 and glioma stem cells T3691 and athymic nude mice with intracranial glioma were selected as our in vitro and in vivo model. IL-13-liposomes-Gd/DTPA-Dox was developed and characterized. Its application in vitro and in vivo has been evaluated through targeted MRI guided drug delivery. Our results provided the evidence that corresponded with our hypothesis. We predicted that the development of IL-13-liposomes-Gd/Dox will not only lead a translation into clinical neuro-oncology, but also into treatment of other tumors like colon cancer metastasis and adrenocortical carcinoma, which overexpressed IL-13Rα2.