Extended Data Fig. 5: Intraperitoneal dosing of 20 µg of Mal-LbL NPs does not cause systemic toxicity.
From: IL-12-releasing nanoparticles for effective immunotherapy of metastatic ovarian cancer
a, healthy B6C3F1 mice were treated on days 0 and 7 with 20 µg of IL-12 as a free cytokine or conjugated to Mal LbL-NPs. Shown are the percentage change of body weight. b-c, B6C3F1 mice (1 cohort n = 5 animals/group) inoculated with 106 HM-1-luc tumor cells on day 0 were treated on days 7 and 14 with 20 µg of IL-12 as a free cytokine or conjugated to Mal-LbL NPs. Serum was collected from mice one day before dosing as well as 24, 48 and 72 hrs after dosing. Shown are quantitation of serum IL-12 (b) and serum IFN-γ (c). d-h, B6C3F1 mice inoculated with 106 HM-1 tumor cells on day 0 were treated on days 10 with 20 µg of IL-12 as a free cytokine or conjugated to Mal NPs (UL and LbL). Two days after dosing blood (n = 5-6/group) and spleens (n = 4/group) were harvested and sent for a complete blood panel or processed for flow cytometry analysis, respectively. Shown are serum levels of liver damage markers (alanine transaminase – ALT - and aspartate aminotransferase - AST) compared to healthy mice controls (n = 4, d), complete blood count panel (e), quantitation of live leukocyte (CD45+) counts in spleen (f), and percentage of macrophage (g), NK (h) cell in splenocytes. Statistical comparisons performed using two-way (d, e) or one-way (f, g, h) analysis of variance (ANOVA) with Tukey’s multiple-comparisons (liver enzyme measurement was compared to healthy controls). In all panels, each point corresponds to a single animal, with values shown as mean ± standard deviation.
