The Study On Biomimetic Metal Organic Framework-mediated Combined Tumor Therapy

According to reports,it is estimated that by 2021,there will be 1.89 million new cancer cases and 600 thousand cancer deaths in the United States.For complex diseases like cancer,a single treatment strategy is often not enough.Current treatment strategies gradually tend to multi-pronged combination therapy to make cancer treatment more effective and thorough.In this paper,we discussed the effect of combination therapy mediated by a multifunctional nanotherapy platform based on biomimetic metal-organic framework(MOF)combined with photothermal therapy(PTT),Fenton therapy,and chemotherapy in the treatment of cancer.The specific research content is as follows:A metal-organic framework nanoparticle rich in iron ions was constructed,in which iron ions participate in the Fenton reaction as nanoenzymes to catalyze endogenous hydrogen peroxide to generate the strongest reactive oxygen radicals(·OH)for killing tumors.This treatment mechanism has become a new strategy for cancer treatment.However,due to the heterogeneity of tumor tissues and insufficient endogenous hydrogen peroxide,the treatment efficiency of Fenton’s reaction will be greatly limited.Precise photothermal therapy(PTT)can solve this problem by increasing the temperature to catalyze the Fenton reaction.In this study,a combination therapy platform based on the Fenton reaction mediated by metal organic framework with iron ions was developed,namely PPy-CTD@MIL-100@MPCM nanoparticles(PCMM NPs),and the inhibitory effect of PCMM NPS on heat shock response(HSR)was also investigated.PCMM NPs can be recruited into tumour tissues through the response of biomacromolecules on the surface of macrophage cell membranes(MPCMs)to tumour cell signaling molecules,thereby increasing retention and accumulation in tumor tissue.The core of PCMM NPs is polypyrrole(PPy).The efficient photothermal effect of PPy can not only cause thermal ablation of tumors,but also enhance the reaction efficiency of Fenton’s reaction due to the increased local temperature.Although photothermal therapy and Fenton’s response trigger the tumor’s own protective mechanism-heat shock response,the cantharidin(CTD)loaded in PCMM NPs can inhibit this response to a large extent.In addition,the heat generated during the PTT process can accelerate the release of iron ions from PCMM NPs and improve the efficiency of the Fenton reaction.PCMM NPs can realize the combination of tumor PTT,Fenton therapy and chemotherapy.Both in vivo and in vitro studies have demonstrated that the combination therapy can kill more than 90%of tumor cells within the skin tolerance threshold(330-1000 m W/cm~2).Finally,we also investigated the effect of PCMM NPS on the inhibition of HSR in photothermal therapy,and found that 14.5g/m L CTD could effectively inhibit HSR in tumor cells.In conclusion,PCMM can be used as a promising nano-drug delivery system for combination therapy of cancer in the future,providing a new strategy for the treatment of cancer.