Title |
Targeting brain tumors by intra-arterial delivery of cell-penetrating peptides: a novel approach for primary and metastatic brain malignancy
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Published in |
Journal of Neuro-Oncology, September 2017
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DOI | 10.1007/s11060-017-2615-5 |
Pubmed ID | |
Authors |
Shailendra Joshi, Johann R. N. Cooke, Jason A. Ellis, Charles W. Emala, Jeffrey N. Bruce |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Scientists | 1 | 50% |
Members of the public | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 20 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Doctoral Student | 4 | 20% |
Student > Ph. D. Student | 3 | 15% |
Student > Master | 2 | 10% |
Researcher | 2 | 10% |
Professor | 1 | 5% |
Other | 2 | 10% |
Unknown | 6 | 30% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 5 | 25% |
Neuroscience | 2 | 10% |
Agricultural and Biological Sciences | 1 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Biochemistry, Genetics and Molecular Biology | 1 | 5% |
Other | 1 | 5% |
Unknown | 9 | 45% |