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these bonds are stable at physiological pH (7.4) but hydrolyze rapidly in acidic conditions ( Polymeric materials: Poly (β-amino esters), poly (methacrylic acid), histidine-modified polymers, which undergo protonation-induced charge reversal or hydrophobic–hydrophilic transition in acidic endosomes ( Inorganic carriers: CaCO3, ZnO, and mesoporous silica nanoparticles (MSN) with pH-degradable gatekeepers ( These materials enable rapid drug release in bladder cancer cells, enhancing cytotoxicity and inhibiting proliferation ( 2.2.1.2 Enzyme-responsive mechanism Matrix metalloproteinases (MMP-2/9) are overexpressed in bladder cancer, serving as biological triggers