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. Author manuscript; available in PMC: 2020 Jul 1.
Published in final edited form as: Clin Cancer Res. 2019 Sep 12;26(1):147–158. doi: 10.1158/1078-0432.CCR-19-1834

Figure 6. Distribution of Dasatinib-NDC in GBM and effective inhibition of downstream PDGFR-β signaling.

Figure 6.

a) RCAS/tv-a tumor bearing mice were treated with RGD-targeted Das-nanoparticle conjugate (cRGD-Das-NDC, red, top row) or non-targeted nanoparticle drug conjugate (cRAD-Das-NDC, red, bottom row) and sacrificed at 96 hours post-treatment. Injection of FITC-Dextran (green) and Hoechst (blue) occurred 3 hours and 10 minutes prior to sacrifice, respectively. Frozen sections were imaged using fluorescence microscopy. Representative samples demonstrate Cy5 distribution and retention consistent with previous studies of non-drug conjugated particle. Panels 1-4: cRGD-Das-NDC treated mGBM demonstrating H&E (1) and corresponding Hoechst (2), FITC (3) and Cy5 (5) distributions. Similarly, Panels 5-8 show a representative cRAD-Das-NDC treated mGBM with H&E (5), Hoechst (6), FITC (7) and Cy5 (8) distributions. b) mGBM animals were treated with a single dose of 45 μM cRGD-Das-NDC dose (top row), or left untreated (bottom row), and sacrificed 24 hours later. Frozen brain tumor sections were evaluated for cRGD-Das-NDC therapeutic efficacy by p-S6RP immunohistochemistry. Clear reduction of p-S6RP intensity was observed following administration of cRGD-Das-C’ Dot. C) Quantification of p-S6RP tumor staining intensity across all control (n=5) and cRGD-Das-NDC treated tumors (n=6). Displayed are the results of the evaluation of 5 high power fields per tumor (Student’s T-test, * p = 0.0212).