Herein,the nanoscaled ATP-responsive upconversion metal-organic frameworks (UCMOFs) are aqueous-phase synthesized for co-delivery of therapeutic protein cytochrome c (Cyt c) and chemodrugs doxoru-bicin (DOX),achieving targeted combinational therapy of human cervical cancer.The UCMOFs are ra-tionally fabricated by growing ZIF-90 on mesoporous silica-coated upconversion nanoparticles (UCNPs),in which the ZIF-90 layer attenuates the upconversion luminescence (UCL) and the rigid frameworks in-crease the stability of encapsulated proteins.Once the UCMOF@DOX/Cyt c are internalized into HeLa cells via specific recognition of sgc8 aptamers,the intracellular ATP triggers the dissolution of ZIF-90 into Zn2+,which facilitates not only the release of Cyt c and DOX but also the restoration of UCL for real-time mon-itoring of drug release.It has been demonstrated that the therapeutic efficacy is greatly improved by the combination of caspase-mediated apoptosis activated by Cyt c (protein therapeutics),DNA fragmentation induced by DOX (chemotherapy),and Zn2+-promoted generation of reactive oxygen species (ROS) (ox-idative stress).Overall,our proposed multifunctional UCMOFs provide an effective platform for targeted combinational cancer therapy and in situ imaging,which hold great promise in biomedical and clinical applications.