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Journal of Neuro-Oncology

, Volume 135, Issue 3, pp 497–506 | Cite as

Targeting brain tumors by intra-arterial delivery of cell-penetrating peptides: a novel approach for primary and metastatic brain malignancy

  • Shailendra JoshiEmail author
  • Johann R. N. Cooke
  • Jason A. Ellis
  • Charles W. Emala
  • Jeffrey N. Bruce
Laboratory Investigation
First Online:

Abstract

Computational modeling shows that intra-arterial delivery is most efficient when the delivered drugs rapidly and avidly bind to the target site. The cell-penetrating peptide trans-activator of transcription (TAT) is a candidate carrier molecule that could mediate such specificity for brain tumor chemotherapeutics. To test this hypothesis we first performed in vitro studies testing the uptake of TAT by one primary and three potentially metastatic brain cancer cell lines (9L, 4T-1, LLC, SKOV-3). Then we performed in vivo studies in a rat model where TAT was delivered either intra-arterially (IA) or intravenously (IV) to 9L brain tumors. We observed robust uptake of TAT by all tumor cell lines in vitro. Flow cytometry and confocal microscopy revealed a rapid uptake of fluorescein-labeled TAT within 5 min of exposure to the cancer cells. IA injections done under transient cerebral hypoperfusion (TCH) generated a four-fold greater tumor TAT concentration compared to conventional IV injections. We conclude that it is feasible to selectively target brain tumors with TAT-linked chemotherapy by the IA-TCH method.

Keywords

Adjuvant therapy Chemotherapy Glioblastoma Glioma Targeted therapy 
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Notes

Funding

The funding was provided by National Cancer Institute at the National Institutes of Health (Grant No. RO1-CA-138643).

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© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Shailendra Joshi
    • 1
    Email author
  • Johann R. N. Cooke
    • 1
  • Jason A. Ellis
    • 2
  • Charles W. Emala
    • 1
  • Jeffrey N. Bruce
    • 2
  1. 1.Department of Anesthesiology, College of Physicians and SurgeonsColumbia University Medical CenterNew YorkUSA
  2. 2.Department of Neurological SurgeryColumbia University Medical CenterNew YorkUSA

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