Development Of Near-infrared Ⅱ Plasmonic MOFs Nano-Drug Carriers And Their Therapeutic Effect Evaluation

Metal-organic frameworks（MOFs）are considered nano-drug carriers with great potential due to their various pore structure types.Through near-infrared region Ⅱ（NIR-Ⅱ）plasmonic optical function materials,MOFs have more cancer treatment functions apart from drug loading,which can meet complex cancer treatment application scenarios.Due to the limitation of material preparation technology and selection of optical function materials,related plasmonic MOFs nano-drug carriers are still unable to encapsulate drug molecules efficiently and multifunctional treatment.Thus,the research targets in this paper were developing the encapsulation technology for molecular drugs in plasmonic MOFs and exploring the multiple therapeutic plasmonic MOFs as drug carriers.The relevant works and achievements are as follows:（1）Two clinical drugs,disulfide,and clopidogrel have been successfully encapsulated by NIR-Ⅱ gold nanorods（Au NRs）to plasmonic cupric zeolite imidazole-8（ZIF-8）MOFs drug carrier（plas CDCu/ZIF-8）.The designed drug carrier can meet the anticancer conditions of the encapsulated drug and improve the utilization rate of the drugs.Under physiological acidity,released Cu²⁺and disulfide were converted to copper diethyldithiocarbamate to cure cancer.Clopidogrel was used to reduce glutathione（GSH）overexpression in cancer cells and amplify the chemodynamic therapy（CDT）effect induced by copper ions.Finally,plas CDCu/ZIF-8 is a synergistic chemo-therapy/CDT/hyperthermia therapy with three-modal treatments and could deliver drugs and treat cancers.（2）Plas En MOFs,an Au NRs plasmonic tri-enzyme（catalase,glucose oxidase,and horseradish peroxidase）integrated ZIF-8 MOFs nano-drug,was prepared.Plas En MOFs solved the problem that the natural enzyme cascade is hard for clinical application due to the loss of activity during the transporting in vivo.The improved chemo-and thermo-tolerance of the encapsulated natural enzymes within the protective ZIF-8 MOFs is verified.As a tri-enzyme cascade system,the plas En MOFs effectively increase catalytic efficiency by four times combined with the plasmonic hyperthermia therapy.Prove the enhanced glucose consumption and ROS generation by the NIR-Ⅱ photothermal.With the integrated enzyme cascades and photothermal,plas En MOFs are verified with therapeutic effects in vivo through combined starvation/CDT/hyperthermia therapy.（3）Glutathione（GSH）-degradable Cu_2-xTenanosheets with PEG-ylation(bio Cu_2-xTeNSs)as a multifunctional CDT agent is prepared for cancer treatment with hyperthermia and redox homeostasis breaking.The resulting bio Cu_2-xTeNSs exhibit excellent near-infrared Ⅱ（NIR-Ⅱ）plasmonic absorption and photothermal properties.Upon endocytosis by cancer cells,bio Cu_2-xTeNSs are degraded into Cu⁺and Teby GSH overexpressed in cancer.The both generated Cu⁺and Teexhibit efficient catalytic endogenous H₂O₂ into·OH,effective GSH depletion,and redox homeostasis breaking of cancer cells.The hyperthermia from the NIR-Ⅱ irradiation can promote intracellular·OH production and tumor accumulation of the drug.Due to these prominent features,in vitro and in vivo results verify the remarkable therapeutic efficacy of bio Cu_2-xTeNSs under NIR-Ⅱ irradiation as a multifunctional plasmonic drug.（4）Cu_2-xTenanosheets developed in the experiment were further used to multi-functionalized ZIF-8 MOFs and adsorb hyaluronic acid（HA）with cancer targeting function on the surface to form a multifunctional therapy-delivery integrated carrier(HACu_2-xTe-MOFs).Under the conditions of hyaluronidase degradation and p H degradation,HACu_2-xTe-MOFs can release Cu_2-xTeNSs and result in treatment.Preliminary cancer cell studies have demonstrated that HACu_2-xTe-MOFs have higher safety and therapeutic efficacy than bio Cu_2-xTeNSs.With the NIR-Ⅱ photothermal effect,HACu_2-xTe-MOFs have outstanding cancer therapy.