Figure 6.
Antitumor efficacy of venetoclax as free drug and encapsulated into nanoparticles. (A) Representative atomic force microscopy images of venetoclax-NP. Size of the nanoparticles is depicted in a colorimetric scale from yellow (80 nm) to dark purple (0 nm). (B) Ex vivo images of tumor (SU-DHL-6), heart, kidney, spleen, and liver on day 14 from a mouse that had venetoclax nanoparticles administered. Note the specific localization of the nanoparticles to tissues (tumor and the lungs) that express P-selectin. (C) Quantification of nanoparticle biodistribution in organs and tumor (SU-DHL-6), calculated from ex vivo fluorescence images shown in panel C as total fluorescence efficiency divided by tissue area (n = 2) (error bars represent SD). Statistical significance relative to vehicle was calculated by a Mann-Whitney U test. (D) DLBCL SU-DHL-6 cells were xenografted subcutaneously into NSG female mice. After 8 days, mice were randomly assigned into comparable groups (5 mice each) and were treated with vehicle, S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), venetoclax-NP (25 mg/kg IV 3 times per week), combinations of S63845 (12.5 mg/kg IV 3 times per week) and venetoclax (25 mg/kg orally 3 times per week) and venetoclax-NP (25 mg/kg orally 3 times per week), and venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week) for 2 weeks (indicated by black line). (E) DLBCL U-2973 cells were xenografted subcutaneously into NSG female mice. After 10 days, mice were randomly assigned into comparable groups (5 mice each) and treated with vehicle, S63845 (25 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 5 times per week), IR-783 and venetoclax-NP (25 mg/kg IV 3 times per week), combinations of S63845 (25 mg/kg IV 3 times per week) and venetoclax (25 mg/kg orally 5 times per week), and a combination of IR-783 and venetoclax-NP (25 mg/kg orally 3 times per week) and S63845 (25 mg/kg IV 3 times per week) for 2 weeks (indicated by black line). Tumor volumes are represented as means; error bars represent SD. Statistical difference between tumor group and vehicle at each time point is calculated by 2-way ANOVA. ****P < .0001; ***P < .001; **P < .01.

Antitumor efficacy of venetoclax as free drug and encapsulated into nanoparticles. (A) Representative atomic force microscopy images of venetoclax-NP. Size of the nanoparticles is depicted in a colorimetric scale from yellow (80 nm) to dark purple (0 nm). (B) Ex vivo images of tumor (SU-DHL-6), heart, kidney, spleen, and liver on day 14 from a mouse that had venetoclax nanoparticles administered. Note the specific localization of the nanoparticles to tissues (tumor and the lungs) that express P-selectin. (C) Quantification of nanoparticle biodistribution in organs and tumor (SU-DHL-6), calculated from ex vivo fluorescence images shown in panel C as total fluorescence efficiency divided by tissue area (n = 2) (error bars represent SD). Statistical significance relative to vehicle was calculated by a Mann-Whitney U test. (D) DLBCL SU-DHL-6 cells were xenografted subcutaneously into NSG female mice. After 8 days, mice were randomly assigned into comparable groups (5 mice each) and were treated with vehicle, S63845 (12.5 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 3 times per week), venetoclax-NP (25 mg/kg IV 3 times per week), combinations of S63845 (12.5 mg/kg IV 3 times per week) and venetoclax (25 mg/kg orally 3 times per week) and venetoclax-NP (25 mg/kg orally 3 times per week), and venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week) for 2 weeks (indicated by black line). (E) DLBCL U-2973 cells were xenografted subcutaneously into NSG female mice. After 10 days, mice were randomly assigned into comparable groups (5 mice each) and treated with vehicle, S63845 (25 mg/kg IV 3 times per week), venetoclax (25 mg/kg orally 5 times per week), IR-783 and venetoclax-NP (25 mg/kg IV 3 times per week), combinations of S63845 (25 mg/kg IV 3 times per week) and venetoclax (25 mg/kg orally 5 times per week), and a combination of IR-783 and venetoclax-NP (25 mg/kg orally 3 times per week) and S63845 (25 mg/kg IV 3 times per week) for 2 weeks (indicated by black line). Tumor volumes are represented as means; error bars represent SD. Statistical difference between tumor group and vehicle at each time point is calculated by 2-way ANOVA. ****P < .0001; ***P < .001; **P < .01.

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