Drug Crrier Construction And Antitumor Performance Studies Base On Modified Zeolitic Imidazolate Framework-8

Osteosarcoma is the most common malignancy and its effects on children and adolescents are much higher than other populations.Current clinical treatments including radiation,chemotherapy and tumor resection have enabled patients to achieve 5-year survival rates of more than 65%,while for advanced and metastatic osteosarcoma,survival rates are as low as 20%.In addition,as with other cancers,osteosarcoma has a tendency to invade and metastasize early,which reduces the treatment effect of patients.At present,effective chemotherapeutic drugs for treating osteosarcoma include adriamycin,methotrexate,and cisplatin.However,these drugs have strong toxic and side effects,and tumors have evolved resistance to them.Therefore,new treatment methods are urgently needed.In addition,the activity of herbal on tumor has attracted more and more attention.However,it has weak toxicity to tumor.With the development of nanotechnology,biomedical nanotechnology has become a multi-purpose method.Nanoparticles as a drug delivery system can accumulate at the tumor site and increase the bioavailability of drugs through the enhanced permeability and retention(EPR)effect,and they can also be modified in various ways to achieve multiple approaches to tumor treatment.Zeolitic imidazolate framework(ZIF-8)is a new type of porous material,which has higher drug loading capacity,excellent biocompatibility and pH-sensitive than traditional nanoparticles delivery system.ZIF-8 NPs can passively target tumor sites,which can reduce the toxic and side effects of chemotherapeutic drugs on normal tissues and enhance the toxicity of drugs to tumors.(1)In this work,chemotherapeutic drugs were confined to the ZIF-8 by in situ packaging,and the particle size of ZIF-8 was adjusted using the triethylamine.The smaller nano-particle size facilitates the accumulation of nanoparticles at the tumor site through the EPR effect,and ZIF-8 pH-responsive behavior made the drug release at tumor site.These properties avoided methotrexate exposure in normal tissues and reduced side effect.Oxidative polymerization of polydopamine on ZIF-8 surface can be used in synergistic chemo-and photothermal therapy to treat osteosarcoma.The results of MTT,dead/live staining,LDH,and cell morphology observation show that the introduction of photothermal agent enhances the antitumor effect and reduces the dose of chemotherapeutic drugs.In addition,JC-1 and DCFHDA staining were used to analyze the effects of the samples on mitochondrial membrane potentials of MG63 and ROS.(2)In our work,18β-glycyrrhetinic acid(GA)was restricted to ZIF-8 by in situ packaging.This method of preparing GA@ZIF-8 improves the entrapment efficiency and bioavailability of 18β-glycyrrhetinic acid.In order to improve the biocompatibility of ZIF-8 NPs,we modified the hyaluronic acid-allen phosphate(HA-ALN)conjugate on the GA@ZIF-8 NPs surface to prepared HA-ALN/GA@ZIF-8 NPs.HA-ALN/GA@ZIF-8 NP was measured by TEM,XRD and FTIR.In addition,the drug loading of HA-ALN/GA@ZIF-8 NPs was determined the by UV-vis,The drug loading efficiency is 12.17%.In vitro experiment were used to evaluate the anti-tumor ability of HA-ALN/GA@ZIF-8 NPs.MTT,LDH,live/dead and Phalloidin staining confirm that HA can target MG63 cells effectively.Mitochondrial fluorescent probes JC-1 staining showed that the GA cause mitochondrial dysfunction.The as-obtained materials can target tumors,has promising applications in the treatment of osteosarcoma.