Herein,the nanoscaled ATP-responsive upconversion metal-organic frameworks(UCMOFs)are aqueousphase synthesized for co-delivery of therapeutic protein cytochrome c(Cyt c)and chemodrugs doxorubicin(DOX),achieving target...Herein,the nanoscaled ATP-responsive upconversion metal-organic frameworks(UCMOFs)are aqueousphase synthesized for co-delivery of therapeutic protein cytochrome c(Cyt c)and chemodrugs doxorubicin(DOX),achieving targeted combinational therapy of human cervical cancer.The UCMOFs are rationally 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 increase 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 Zn^(2+),which facilitates not only the release of Cyt c and DOX but also the restoration of UCL for real-time monitoring 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 Zn;-promoted generation of reactive oxygen species(ROS)(oxidative 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.展开更多
基金the support from the National Natural Science Foundation of China(Nos.21834004 and 22076087)the Special Funds of the Taishan Scholar Program of Shandong Province(No.tsqn20161028)+2 种基金the Natural Science Outstanding Youth Fund of Shandong Province(No.ZR2020JQ08)the Youth Innovation Technology Program of Shandong Province(No.2019KJC029)the Program B for Outstanding PhD Candidate of Nanjing University(No.201902B069)。
文摘Herein,the nanoscaled ATP-responsive upconversion metal-organic frameworks(UCMOFs)are aqueousphase synthesized for co-delivery of therapeutic protein cytochrome c(Cyt c)and chemodrugs doxorubicin(DOX),achieving targeted combinational therapy of human cervical cancer.The UCMOFs are rationally 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 increase 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 Zn^(2+),which facilitates not only the release of Cyt c and DOX but also the restoration of UCL for real-time monitoring 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 Zn;-promoted generation of reactive oxygen species(ROS)(oxidative 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.
