Functional Design Of Metal-Azolate Frameworks And Its Application In Cancer Therapy

Cancer is a severe threat to human health in the world.However,due to the complexity,diversity and heterogeneity of tumors,the current clinical treatment of tumors has received very limited success.Clinically,radiotherapy,chemotherapy,operation and emerging immunotherapy are the common treatments to wipe out tumors.However,these therapeutics often have somedrawbacks,for instance,surgical excision can only slightly eradicate tumors,but the metastasis of the tumor is often induced by the failure of the surgical treatment.Radiotherapy and chemotherapy cannot distinguishbetween normal and tumor tissues,and usually accompanied with strong side effects.In recent years,with the development of science and technology,the emergence of nanotechnology has provided new flashs for solving these restrictions.Nanotechnology can integrate a variety oftherapies to achieve high efficiency and low toxicity in the treatment of tumors.MAF is a porous materialwhich composed of zinc salt and imidazole self-assembled.Because of its large surface area,unique pore volume and inherent biodegradability,MAF-4 is one of the most promising MOF.Hence,in this paper,we synthesized three kinds of MAF-4 composite nanomaterials : PSe D@MAF-4(R),DOX@DBA@MAF-4,Bi@MAF-4,andhandledwiththe carcinomas by targeting therapy,thermotherapy combined with chemotherapy,radiotherapy and thermotherapy,and studied the effect of the tumor.The results are as follows: 1.PSe D@MAF-4(R)targeting therapyAlthough selenadiazole derivatives(PSe D)exhibit good antitumor activity,most of them have poor solubility in water,which greatly restricts their effect in biological applications.Therefore,in this chapter,we have designed and synthesized a targeted MAF-4 system to promote the water solubility of selenadiazole derivatives,thus enhancing its anti-tumor effect.c RGD molecules and two block polymers PEI-PEG molecules make the system biocompatible and selectivity,then MAF-4 systemcan recognize between normal cells and tumor cells,thus delivering selenadiazole derivatives accurately realizing the controlled release in the tumor cells.As a result,PSe D@MAF-4(R)showed strong anti-tumor effectin vitro and in vivo.2.DOX@DBA@MAF-4 chemotherapy combined with thermotherapyChemotherapy is one of the most decisive ways to treat tumors,but the traditional chemotherapeutic drugs,for instance,Doxorubicin(DOX),often need high doses for the better treatment of tumors,and the toxic problem caused by the drug is always a troublesome problem.Photothermal therapy is a simple and efficient wayto deal with tumor,which has little damage to normal cells.Therefore,that one mayfigure out the problem of toxicitycreated by DOX,we have combined photothermal therapy with chemotherapy,aimd to reduce the dosage of drugs,and treat carcinomas by high efficiency and low toxicity approachs.In this chapter,we have designd and synthesized a DOX@DBA@MAF-4 nanosystem,which combines the rigidity and stability of MAF-4 good dimensional characteristics.In vitro photothermal effect showed that DBA@MAF-4 had excellent photothermal effect and the conversion efficiency was 29.6%.For example,DBA@MAF-4 nanomaterial can rise to 67 degrees in 2 min,and they still maintain excellent photothermal propertiesafter 5 thermal cycles.DOX was loaded with 98%.Cell viability showed that DOX@DBA@MAF-4 hyperthermia combined with chemotherapy was more effective than chemotherapy alone,and there was no obvious demage to normal cells,which proved that the combination of hyperthermia and chemotherapy had excellent antitumor effect.3.Bi@MAF-4 radiotherapy and hyperthermiaOwing to the excellence of the photothermal therapy system,we hope to continue comprehensive research.The research shows that bismuth nanomaterials have low toxicity and high photothermal conversion efficiency,which used as an excellent photothermal material.Radiotherapy,as a way of eliminate tumors,often results in failure of radiotherapy because of lack of oxygen in tumor cells.Peroxidase(CAT)can catalyze the production of oxygen by peroxide,but it is unstable and easy to be dispose of in circulation in vivo.In view of the characteristics of hypoxia and a large number of peroxides,we hope to combine the properties of the bismuth quantum dots in this chapter by combining the MAF-4 loaded peroxidase(CAT)to the combination of radiation therapy and thermotherapy.In this chapter,we have adopteda straightforward synthesis approach to synthesize Bi@MAF-4 composites in one step.PXRD results show that the crystal shape of the composite nanoparticles is not damaged by the addition of Bi.Then the photothermal effect of Bi@MAF-4 is evaluated,it can rise to 70 degrees in three minutes,and efficiency can reach 28.01%.After 5 tests,the heating effect will not change,indicating that it has good stability.The experiment of Bi@MAF-4 composite loading peroxidase(CAT)is in progress.