Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors

Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression...

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Bibliographic Details
Published in:PloS one 2018-01, Vol.13 (1), p.e0181529-e0181529
Main Authors: Madhankumar, A B, Mrowczynski, Oliver D, Slagle-Webb, Becky, Ravi, Vagisha, Bourcier, Alexandre J, Payne, Russell, Harbaugh, Kimberly S, Rizk, Elias, Connor, James R
Format: Article
Language:English
Subjects:
Apoptosis
Binding sites
Biology and Life Sciences
Biotechnology
Cancer therapies
Cell adhesion & migration
Cell culture
Consent
Cytotoxicity
Doxorubicin
Glioblastoma
Immunohistochemistry
In vivo methods and tests
Interleukin 1
Interleukin 13
Invasiveness
Medical schools
Medicine
Medicine and Health Sciences
Neurosurgery
Peripheral nerves
Polyethylene glycol
Receptors
Research and Analysis Methods
Sciatic nerve
Sheaths
Studies
Tumors
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Summary:Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0181529