(A) Relationship between percent hemolysis at pH 6.2 and IL-1β secretion after treatment with 40 μg/mL for 4 hours demonstrates there is not a correlation between hemolytic activity and inflammasome activation. (B) Relationship between percentage of lysosomal rupture after 4 hours and IL-1β secretion after treatment with polymers at 40 μg/mL for 4 hours reveals a positive correlation between lysosomal rupture and inflammasome activation. (C) Data support a working hypothesis that PEG-b-(DMAEMA-co-BMA) polymers with 50–60% BMA (50B and 60B) are endocytosed, and disassemble at early endosomal pH values to mediate disruption the endosomal membrane, resulting in release of cargo into the cytosol. By contrast, polymers containing 0–40% BMA do not have enough BMA to actively solvate endosomal membranes, instead trafficking to lysosomal compartments, where they ultimately induce lysosomal rupture and release of cathepsins, which contributes to inflammasome activation and secretion of IL-1β.