Figure 1.
Physicochemical characteristics, itaconate release and bio/cell distribution of ITA-LNPs. (A) Schematic of ITA synthesis in biological systems. Selected biological actions of endogenous and exogenous ITA are depicted in blue. (B) Synthesis of ITA-LNPs using phosphatidyl glycerol as a starting material. (C) Dynamic light scattering analysis of ITA-LNP. (D) Time course of ITA release from ITA-LNPs incubated with liver microsomes ex vivo. (E) Quantitative polymerase chain reaction analysis of Acod1 mRNA expression over time in macrophages exposed to 1-μM ITA-LNP. (F) Biodistribution analysis in isolated bone femurs of C57BL/6 mice injected with a bolus IV with 50 mg/kg ITA-LNPs (Atto647 labeled) or PBS and euthanized 4 hours after injection. (G) Quantification of fluorescence from experiments in panel F. (H) FACS gating strategy and analysis of single cells from the bone marrow in panel F. (I) Quantification of cell-specific distribution of ITA-LNPs in the bone marrow; n = 3 animals per group or n = 4 for in vitro experiments. Statistics: pairwise t test with Holm post hoc test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. PBS, phosphate-buffered saline; SDHA, succinate dehydrogenase complex flavoprotein subunit A; TCA, tricarboxylic acid cycle.

Physicochemical characteristics, itaconate release and bio/cell distribution of ITA-LNPs. (A) Schematic of ITA synthesis in biological systems. Selected biological actions of endogenous and exogenous ITA are depicted in blue. (B) Synthesis of ITA-LNPs using phosphatidyl glycerol as a starting material. (C) Dynamic light scattering analysis of ITA-LNP. (D) Time course of ITA release from ITA-LNPs incubated with liver microsomes ex vivo. (E) Quantitative polymerase chain reaction analysis of Acod1 mRNA expression over time in macrophages exposed to 1-μM ITA-LNP. (F) Biodistribution analysis in isolated bone femurs of C57BL/6 mice injected with a bolus IV with 50 mg/kg ITA-LNPs (Atto647 labeled) or PBS and euthanized 4 hours after injection. (G) Quantification of fluorescence from experiments in panel F. (H) FACS gating strategy and analysis of single cells from the bone marrow in panel F. (I) Quantification of cell-specific distribution of ITA-LNPs in the bone marrow; n = 3 animals per group or n = 4 for in vitro experiments. Statistics: pairwise t test with Holm post hoc test. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. PBS, phosphate-buffered saline; SDHA, succinate dehydrogenase complex flavoprotein subunit A; TCA, tricarboxylic acid cycle.

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