Figure 6.

Particle size and morphology: inflammasome activation. (A) Particles with spiky morphologies can disrupt endo/phagosomal membranes leading to K⁺ and cathepsin leakage into the cytosol (so-called signal 2). Mitochondrial destabilization causes cytochrome C release leading to cytotoxicity. These stimuli activate inflammasome assembly from caspase-1, ASC, and NLRP3 which cleaves pro-IL-1β and pro-IL-18 into mature IL-1β and IL-18. Inflammasome activation can trigger cell death (pyroptosis). (B) Particle shape is an agonist in particle-based vaccination. Administration of TiO₂ spiky particles initiating mechanical rapture of phagosomes (signal 2) in mice together with a bacterial TLR ligand (signal 1). TLR signaling activates NF-κB relocation to the nucleus leading to pro-IL-1β and pro-IL-18 transcription and translation and upregulation of activation markers CD40, CD80, and CD86. Signal 2 initiates inflammasome-mediated proteolytic conversion into mature IL-1β and IL-18. Mice receiving a combination of spiky particles and a TLR-ligand thereby induce a potent Th1 response.