Fig. 4
Mechanisms of action of lysosome-targeting nanoparticles (NPs) and nanocarriers. a Poly(lactic-co-glycolic acid) (PLGA) NPs will dissociate into their respective component acids, lactic acid (pKa 3.86) and glycolic acid (pKa 3.83), under mildly acidic conditions and directly acidify lysosomes. b Acidic NPs (AcNPs) formed by poly(ethylene tetrafluorosuccinate-co-succinate) will dissociate into their respective component acids, tetrafluorosuccinic acid (pKa 1.63) and succinic acid (pKa 4.20), under mildly acidic conditions and directly acidify lysosomes. c PaNPs are activated upon stimulation by UV light (~ 365 nm), enabling a spatiotemporal control of lysosomal pH by releasing succinic acid. d Acidic nucleolipid nanoemulsions (NL-NEs) are designed to release succinic acid upon enzymatic degradation. Mechanisms of action illustrated are based on the theoretical breakdown of the formed NPs and NL-NEs into their respective component acids. ‘x’ and ‘y’ represent the percentage of each component acid used in the synthesis process. Schematics were created by BioRender and chemical structures were drawn by ChemDraw.