Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors

Achuthamangalam Madhankumar, Oliver D. Mrowczynski, Becky Slagle-Webb, Vagisha Ravi, Alexandre J. Bourcier, Russell Payne, Kimberly Harbaugh, Elias Rizk, James Connor

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0181529
JournalPloS one
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

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doxorubicin
peripheral nerves
Interleukin-13 Receptors
Neurilemmoma
Doxorubicin
Tumors
Sciatic Nerve
neoplasms
Nerve Sheath Neoplasms
Interleukin-13
Neoplasms
receptors
Tumor Cell Line
nerve tissue
Peripheral Nervous System Neoplasms
Immunohistochemistry
cell lines
Cells
Glioblastoma
Luciferases

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Madhankumar, A., Mrowczynski, O. D., Slagle-Webb, B., Ravi, V., Bourcier, A. J., Payne, R., ... Connor, J. (2018). Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors. PloS one, 13(1), [e0181529]. https://doi.org/10.1371/journal.pone.0181529
Madhankumar, Achuthamangalam ; Mrowczynski, Oliver D. ; Slagle-Webb, Becky ; Ravi, Vagisha ; Bourcier, Alexandre J. ; Payne, Russell ; Harbaugh, Kimberly ; Rizk, Elias ; Connor, James. / Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors. In: PloS one. 2018 ; Vol. 13, No. 1.
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Madhankumar, A, Mrowczynski, OD, Slagle-Webb, B, Ravi, V, Bourcier, AJ, Payne, R, Harbaugh, K, Rizk, E & Connor, J 2018, 'Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors', PloS one, vol. 13, no. 1, e0181529. https://doi.org/10.1371/journal.pone.0181529

Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors. / Madhankumar, Achuthamangalam; Mrowczynski, Oliver D.; Slagle-Webb, Becky; Ravi, Vagisha; Bourcier, Alexandre J.; Payne, Russell; Harbaugh, Kimberly; Rizk, Elias; Connor, James.

In: PloS one, Vol. 13, No. 1, e0181529, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Madhankumar, Achuthamangalam

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Madhankumar A, Mrowczynski OD, Slagle-Webb B, Ravi V, Bourcier AJ, Payne R et al. Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors. PloS one. 2018 Jan 1;13(1). e0181529. https://doi.org/10.1371/journal.pone.0181529