Construction Of Two NMOFs Drug Delivery Systems Based On 2-Aminoterephthalic Acid And Their Synergistic Antitumor Effects

Metal-organic framework materials?MOFs?have a wide range of application values in terms of adsorption,separation,and catalysis.The study of nano-scale metal-organic framework materials as drug-loading systems is becoming a hotspot in research today.Organic nanomaterials and inorganic nanomaterials as drug carriers will have the shortcomings of explosive release,large side effects,high biological toxicity,and fast removal speed in the process of drug delivery.Nano metal-organic framework materials?NMOFs?have larger specific surface area,higher stability,and lower biological toxicity,comparing with other metal carriers.In addition,NMOFs will accumulate in the tumor tissues due to their enhanced permeability and retention effect?EPR?,then decompose under the acidic tumor environment.Therefore,it has potential application prospects in the biomedical field.Photodynamic therapy?PDT?is a typical non-invasive and photo-stimulated treatment mode for clinical treatment of superficial tumors and microbial infections.Nevertheless,the clinical application of PDT is mainly limited by the aggregation tendency,non-selectivity of photosensitizers?PS?and tumor hypoxia.To address these problems,we synthesized two NMOFs as drug loading carriers based on 2-aminoterephthalic acid.?1?First,we synthesized UiO-66-NH₂ as a drug carrier and loaded the prodrug of cisplatin,which is a common chemotherapy drug in its pores?loading rate:9%?.In order to increase the stability,the surface of UiO-66-NH₂@Pt was coated with a layer of silicon dioxide.The photosensitizer Silicon 2,3-naphthalocyanine dihydroxide?SNCD?was bonded to the surface of the silicon dioxide layer using a silicon-oxygen bond?loading rate:7%?.Finally,the nanoparticles UiO-66-NH₂@Pt@SiO₂@SNCD were obtained.The drug-loaded nanoparticles can be targetedly delivered to the desired tissues with controlled release due to its response to the acidic tumor environment.The degree of drug release reaches 71.3%within 80h.In the process of photodynamic therapy,SNCD will produce cytotoxic singlet oxygen after being irradiated with a laser of a specific wavelength.Thereby cooperating with cisplatin to kill tumor cells.?2?We have synthesized MIL-101?Fe?-NH₂ using 2-aminoterephthalic acid as a main ligand and tetra?4-carboxyphenyl?porphine?TCPP?as an auxiliary ligand.Therefore,the nanocarriers already have photosensitivity without additional modification of the photosensitizer.Then we loaded tirapazamine?TPZ??loading rate:36%?in the MIL-101?Fe?-NH₂ channel to respond to the hypoxic tumor environment.cRGD targets were subsequently modified on the surface of MIL-101?Fe?-NH₂,which can targetedly reach the lesion site where integrin?_??₃ is highly expressed,in order to prevent ineffective accumulation of drugs and photosensitizers in the body and improve their distribution in tumor tissues.The cytotoxicity experiments indicated that the combination of chemotherapy and photodynamic therapy is a more effective therapy model than single chemotherapy and photodynamic therapy.The results show that:we have designed and synthesized two novel NMOFs drug-loading systems.These drug-loading systems provide new ideas for anti-tumor researches,and have great potential value in synergistic photodynamic therapy.