Research On Construction And Therapeutic Properties Of MOFs Nanoplatform With Gas Loading Performance

As a global medical problem in modern society,cancer is a serious threat to human health due to its high morbidity and mortality.Nanoscale metal-organic frameworks（NMOFs）with excellent drug-carrying capacity and biocompatibility have shown promising applications in tumor therapy and have attracted great attention of researchers.Chemotherapy（CT）and photodynamic therapy（PDT）are both important cancer treatments.Among them,photodynamic therapy,a typical non-invasive photoexcitation treatment method,has been used in the clinical treatment of many cancers with the characteristics of high selectivity and less damage to normal tissues.However,the hypoxic environment of the tumor also affects the level of single-linear oxygen production by the photosensitizer,which in turn limits the antitumor efficacy.Therefore,improvement of the hypoxic environment at the tumor site is needed to improve the efficiency of photodynamic therapy.Chemotherapy（CT）is one of the most commonly cancer treatments,but suffers from low bioavailability and suboptimal therapeutic efficacy.Among them,much attention has been paid to the application of depleted oxygen-activated prodrugs,which are chemotherapeutic agents with selective toxicity that require depleted oxygen conditions to activate their anticancer efficacy.However,the level of depleted oxygen within the tumor is often heterogeneous and cannot fully stimulate the pharmacological activity of this class of drugs.Therefore,there is a need to induce and enhance the hypoxic environment at the tumor site to improve the chemotherapeutic efficacy of specific hypoxia-activated prodrugs.Therefore,effective modulation of tumor depleted oxygen microenvironment is important to improve both photodynamic therapy and chemotherapy efficacy.In this thesis,we synthesized two MOF nanoplatforms with both gas and photosensitive molecules or gas and spent oxygen-activated precursors loading properties for photodynamic and chemotherapeutic performance studies in cancer.The details are as follows:（1）Construction of noval MOF nanoplatform co-loaded oxygen-carrying protein and photosensitive molecules for improved PDTIn the work of this chapter,in order to improve the efficacy of oxygen-dependent photodynamic therapy,we exploited the oxygen-carrying property of hemoglobin to achieve effective photodynamic performance enhancement by alleviating the lack of oxygen at the tumor site.We first synthesized nanosized mesoporous Zr-based MOF and loaded both hemoglobin and photosensitizer indocyanine green in its pores to obtained a MOF photosensitized nanoplatform MUi O@Hb-ICG@HA.The experimental results showed that the material could provide additional O₂ in the tumor microenvironment,effectively enhanced the efficacy of photodynamic therapy.（2）Construction of noval MOF nanoplatform co-loaded CO-carrying protein and de-pleted oxygen-activated antitumor precursors for improved chemotherapyIn the work of this chapter,we chose to enhance the hypoxic characteristics of tumor microenvironment to achieve specific chemotherapy efficiency.Based on the hemoglobin-carrying Zr-based MOF synthesized in the previous work,another MUi O@COHb-TPZ@HA nanoplatform were obtained by coloading CO and the hypoxia-activating prodrug tirazamine.The CO released in tumor microenvironment accelerated mitochondrial respiration and intensified hypoxia to further activate tirazamine for improved chemotherapy.All the experimental results showed that MUi O@COHb-TPZ@HA induced more cell apoptosis by releasing CO compared with tilazamine drug only,which effectively achieved chemotherapy potentiation.