Construction Of MOF-based Nnanocatalytic Medicine And Its Application In Tumor Therapy

As a new concept,tumor nanocatalytic therapy refers to a series of therapeutic modalities which base on chemical reaction triggerd by nanocatalytic medicine at the tumor site.However,the therapeutic efficiency of nanocatalytic therapy has been severly restricted by the intrinsic physicochemical properties of tumor microenvironment?TME?,such as hypoxia and limited H₂O₂.Herein,three nanocatalytic medicines based on metal-organic framework were constructed.The asprepared nanocatalytic medicines can modulate TME and further enhance the therapeutic efficiency of combination or synergistic treatment against tumors.?1?By taking advantage of the significant gas-adsorption capability of metal-organic framework,a biomimetic O₂-evolving photodynamic therapy nanocatalytic medicine with long circulating properties was fabricated.Zirconium?IV?-based MOF?UiO-66?was used as a vehicle for O₂ storing,then conjugated with indocyanine green?ICG?by coordination reaction of Zr and-SO₃H,and further coated with red blood cell membranes?RBC?.Upon808 nm laser irradiation,the initial singlet oxygen?¹O₂?generated by ICG would destroy RBC membranes.At the same time,The photothermal property of ICG could facilitate the burst release of O₂ from UiO-66.Subsequently,the generated O₂ could significantly improve the PDT effects on hypoxic tumor.Owing to the advantages of long circulation and O₂self-sufficient,the designed nanotherapeutic agent can improve the efficiency of treatment against hypoxia tumor via PDT.?2?A pH-responsive nanocatalytic medicine,CaO₂@DOX@ZIF-67,was constructed via bottom-up approach,which could increase the concentration of O₂ and H₂O₂ simutaneously in TME.CaO₂ nanoparticles were first prepared with PEG-200 as solvent and template.Then,DOX was coated onto the surface of the CaO₂ via coordination between DOX and Ca to form CaO₂@DOX.To further isolate and protect the CaO₂@DOX from external water,ZIF-67 was finally constructed on the surface of CaO₂@DOX by an in situ synthesis method.The outermost ZIF-67 layer will be disassembled in the acidic environment of tumor due to its pH sensitivity,resulting in rapid release of Co²⁺and DOX.At the same time,the unprotected CaO₂ will react with water to produce O₂ and H₂O₂.The generated H₂O₂ will then be further catalyzed by Co²⁺ions to produce highly toxic·OH through a Fenton-like reaction,while the generated O₂ will improve the efficacy of DOX by alleviating the hypoxic conditions in the tumor.This nanocatalytic medicine provides a novel strategy for improving the effectiveness of combined chemo/chemodynamic therapy.?3?A cascade nanocatalytic medicine,CaO₂@MIL-88B@GOx,was constructed,which can be used for enhancing the synergistic effect of starvation therapy and chemodynamic therapy.CaO₂ nanoparticles were first prepared with polyvinylpyrrolidone as template and protector.To further isolate and protect the CaO₂ from external water,MIL-88B was constructed on its surface by an in situ synthesis method.Then,glucose oxidase?GOx?was adsorbed on the surface of CaO₂@MIL-88B via the coordination effect between GOx and MIL-88B.After accumulation in the tumor region,GOx could decompose endogenous glucose into gluconic acid and H₂O₂.The increased H⁺could accelerate the decompostion reaction of MIL-88B and release Fe³⁺,a Fenton-like catalyst.At the same time,the unprotected CaO₂ will react with water to produce O₂ and H₂O₂.Subquently,Fe³⁺consume H₂O₂ through a Fenton-like reaction to produce highly cytotoxic·OH radicals that killed the tumor cells.While the generatd O₂ can relieve the hypoxia of tumor tissues,and further increase the enzymatic reaction rate of GOx.