Photodynamic therapy (PDT) is a promising strategy for tumor treatment.Still,its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenvironment properties like hypoxia and high glutathione levels.Here,we fabricated a novel nanoenzyme that derived from metal-organic framework (MOF) with intrinsic catalase-like activities to decompose H2O2 to O2 and simultaneous glutathione consumption for enhancing PDT efficacy.The obtained Mn.3O4 nanoparticle shows a larger pore size and surface area compared to native MOF particles,which can be used to load high dose photosensitizer.When decorated with AS1411 aptamer and polyethylene glycol (PEG),the obtained Mn3O4-PEG@C&A particle exhibits excellent stability and cell nucleus targeting ability.Remarkably,Mn3O4-PEG@C&A particle inhibited the tumor growth in the mouse model with high efficacy without any biotoxicity.This is the first report that applied MOF-derived nanoparticle to nucleus-targeted PDT.It may provide a new approach for designing functional nanoenzyme to subcellular organelles-targeted tumor modulation.