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

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.

journal_name

J Neurooncol

authors

Joshi S,Cooke JRN,Ellis JA,Emala CW,Bruce JN

doi

10.1007/s11060-017-2615-5

subject

Has Abstract

pub_date

2017-12-01 00:00:00

pages

497-506

issue

3

eissn

0167-594X

issn

1573-7373

pii

10.1007/s11060-017-2615-5

journal_volume

135

pub_type

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