BBB-permeation in brain
tumor: Imaging and tumor permeation analysis in a mouse model of glioblastoma.
Female BL/6 Mice (n = 3) were inoculated intracranially
with glioblastoma cell line GL261 at 8 weeks of age and measured 3
weeks after inoculation. A comparison of the permeability of P/LLL(40%),
P/LLLAP2, P/LLLB6, P/LLL/D1, P/LLL/AC189, P/LLL/D3, and P/LLL/M4 in
tumor and nontumor tissue from the contralateral brain hemisphere
was carried out. (A) Representative optical imaging data showing nanoconjugate
permeation into the tumor (right) and in the cerebral cortex of the
contralateral hemisphere in the same animal (left). Comparison of
dose 0.25X (0.068 μmol/kg) and dose 1X (0.274 μmol/kg).
Nanoconjugate fluorescence (red), vasculature (green), and cell nuclei
(blue) are shown. (B) Intensity bar-graph for nanoconjugate fluorescence
in tumor tissue. Background is shown in black, P/LLL(40%) (0.25X and
1X) in green, P/LLL/B6 (0.25X and 1X) in orange, P/LLL/AP2 (0.25X
and 1X) in red, P/LLL/D1 (1X) in violet, P/LLL/ACI89 (1X) in blue,
P/LLL/D3 (1X) in brown, and P/LLL/M4 (1X) in dark blue. Average nanoconjugate
fluorescence measurements were obtained from 20 randomly sampled ROIs
outside of the cerebral vasculature (n = 3 with 5
images acquired in each tumor and nontumor tissue sample). All statistical
tests were conducted by one-way ANOVA with Tukey t tests. Significance is indicated with asterisks where * = p < 0.01, ** = p < 0.001, and ***
= p < 0.0001. Error bars represent SEM.