Figure 5.
Antitumor efficacy of S63845 as free drug and encapsulated into nanoparticles. (A-E) In vivo fluorescent images acquired via IVIS in vivo imaging technology 24 hours after drug administration. (A) Control mouse treated with S63845-NP. Because these mice lacked tumors, there was ubiquitous distribution of S63845-NP. (B) S63845 was administered but no fluorescence was observed. (C) S63845 nanoparticles were administered. Note the localization of nanoparticles to the tumor. Lack of fur, such as in the ears and tail, also shows high fluorescence. (D) In vivo images 48 hours after administration of S63845 nanoparticles. (E) Ex vivo images of tumor, heart, kidney, spleen, and liver on the day the mice were euthanized (day 24). Nanoparticles were administered 3 times per week for 2 weeks until 24 hours before the day the mice were euthanized (day 24). Note the specific localization of the nanoparticles to the tumor. (F) Nanoparticle biodistribution in organs and tumor, calculated from ex vivo fluorescence images shown in panel E 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. (G) DLBCL cells from the SU-DHL-6 cell line were xenografted subcutaneously into NSG female mice. After 6 days, mice were randomly assigned to comparable groups (4 or 5 mice each) and treated with vehicle, venetoclax (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), S63845 (12.5 mg/kg IV 3 times per week), combinations of venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week) and S63845 (12.5 mg/kg IV 3 times per week) for 2 weeks (indicated by black line). Tumor volumes are represented as means; error bars represent SD. (H) Dot plots comparing tumor sizes on day 9 and 20 after of S63845 single-agent was injected into tumors in various treatment groups: S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week). Tumor volumes are represented as mean ± SD. Statistical significance relative to vehicle was calculated with a 2-way ANOVA. ***P < .001; **P < .01; *P < .05.

Antitumor efficacy of S63845 as free drug and encapsulated into nanoparticles. (A-E) In vivo fluorescent images acquired via IVIS in vivo imaging technology 24 hours after drug administration. (A) Control mouse treated with S63845-NP. Because these mice lacked tumors, there was ubiquitous distribution of S63845-NP. (B) S63845 was administered but no fluorescence was observed. (C) S63845 nanoparticles were administered. Note the localization of nanoparticles to the tumor. Lack of fur, such as in the ears and tail, also shows high fluorescence. (D) In vivo images 48 hours after administration of S63845 nanoparticles. (E) Ex vivo images of tumor, heart, kidney, spleen, and liver on the day the mice were euthanized (day 24). Nanoparticles were administered 3 times per week for 2 weeks until 24 hours before the day the mice were euthanized (day 24). Note the specific localization of the nanoparticles to the tumor. (F) Nanoparticle biodistribution in organs and tumor, calculated from ex vivo fluorescence images shown in panel E 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. (G) DLBCL cells from the SU-DHL-6 cell line were xenografted subcutaneously into NSG female mice. After 6 days, mice were randomly assigned to comparable groups (4 or 5 mice each) and treated with vehicle, venetoclax (100 mg/kg orally 5 times per week), S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), S63845 (12.5 mg/kg IV 3 times per week), combinations of venetoclax (100 mg/kg orally 5 times per week) and S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week) and S63845 (12.5 mg/kg IV 3 times per week) for 2 weeks (indicated by black line). Tumor volumes are represented as means; error bars represent SD. (H) Dot plots comparing tumor sizes on day 9 and 20 after of S63845 single-agent was injected into tumors in various treatment groups: S63845 (25 mg/kg IV 5 times per week), S63845-NP (12.5 mg/kg IV 3 times per week), and S63845 (12.5 mg/kg IV 3 times per week). Tumor volumes are represented as mean ± SD. Statistical significance relative to vehicle was calculated with a 2-way ANOVA. ***P < .001; **P < .01; *P < .05.

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