Self-sufficient copper peroxide loaded pKa-tunable nanoparticles for lysosome-mediated chemodynamic therapy

•A series of nanoparticles with tunable acid dissociation constant (pKa) values from 5.2 to 6.2 were prepared.•Nanoparticles with lower pKa value exhibited better retention in lysosomes.•Nanoparticles with low pKa values were effectively trapped in lysosomes to decompose enough amount of catalytic ions.•Catalytic ions can convert self-supplied H2O2 into ·OH by a robust Fenton reaction.•The highly reactive ·OH elicited effective lysosomal membrane permeabilization through lipid peroxidation and thus killed tumor cells in a lysosome-mediated pathway.