| Objective: Chemotherapy is a kind of clinical application at present,which can treat a variety of cancers.However,traditional chemotherapeutic drugs are degraded before reaching the tumor area,with low retention rate in tumor,short blood circulation,high drug resistance and toxicity,and poor tissue penetration,which seriously limit the clinical application of drugs in tumor treatment.Therefore,in order to improve the therapeutic efficiency of drugs,reduce the toxic and side effects of drugs on normal tissues,the corresponding drug carrier system is urgently needed.In this paper,the metal-organic framework(MOFs)ZIF-90 with good biocompatibility and p H targeting was used as the drug delivery carrier,and the anticancer drugs methotrexate(MTX),6-mercaptopurine(6MP),5-fluorouracil(5FU)and cytarabine(Ara)were loaded into ZIF-90 materials by one-pot method,respectively.The drug loading of drug@ZIF-90 and the targeted release of p H were detected to obtain an excellent targeted delivery system of anticancer drugs.Methods: In this paper,based on the principle of crystal engineering,a simple and efficient method for preparing ZIF-90 was designed by optimizing the reaction conditions,and the ZIF-90 material with suitable pore size was obtained,and a variety of anticancer drugs were loaded by one-pot loading method.The structure and physicochemical properties were identified by means of powder X-ray diffraction(PXRD),infrared spectrum(IR),scanning electron microscope(SEM),thermogravimetric analysis(TGA),gas adsorption detection and dynamic light scattering(DLS).The drug-loaded samples were modified by drop-by-drop encapsulation method to further improve the targeted drug release performance of the composite particles,and the drug release process under simulated conditions in vitro was tracked and detected by high performance liquid chromatography(HPLC)to verify the targeted release of the drug loading system.The in vitro cell activity and biocompatibility of the composite particles were detected by MTT detection,and the targeted anticancer activity and good biocompatibility of the composite particles were compared and verified by enzyme labeling instrument.Results:(1)By investigating a large number of literatures at home and abroad,comparing and analyzing and improving the conditions,this paper designs an efficient and simple method for preparing ZIF-90 with a yield of up to 95 %;(2)anticancer drugs were loaded by one-pot method,samples of6MP@ZIF-90,(Ara+6MP)@ZIF-90,(5FU+6MP)@ZIF-90 and MTX@ZIF-90@CS were obtained.The drug loading capacity of 6MP and MTX was as high as 502 mg/g and 250 mg/g;(3)the drug loading system loaded with 6MP(6MP@ZIF-90)achieved the full drug release in about 70 h in the acidic environment of simulated cancer tissue,but only 40 % in neutral conditions,and the in vitro release experiment showed the targeted characteristics and controlled release;(4)in the combined drug loading group,the two anticancer drugs in the composite drug loading particles showed the characteristics of targeted release.In the combined drug loading system(Ara+6MP)@ZIF-90,it took 70 h for the two drugs to release all the drugs in acidic environment,and only about 20 % in neutral conditions.The combined drug delivery system(5FU+6MP)@ZIF-90 can release all of the two drugs under acidic conditions,but only about 45 % under neutral conditions;(5)the drug loading system loaded with MTX further enhanced its targeted drug release function after chitosan modification,which was almost completely released in acidic condition for about 100 h,and about 60 % MTX was released in neutral PBS solution at 25 h.All groups successfully achieved the goal of p H targeted drug release;(6)all drug-loaded systems showed good biocompatibility to the normal cell group in the cell experiment in vitro,after adding the concentration of 20 μg/m L,the cell survival rate was more than60 %,and showed good cell viability in a certain range.On the other hand,it showed a certain growth inhibition to cancer cells,and the survival rate of cancer cells gradually decreased with the increase of the concentration of composite particles,showing an obvious concentration dependence.When the drug concentration was increased to 20 μg/m L,the survival rate of several groups of cancer cells was only about 40 %.Through the comparison between normal cells and cancer cells,we can know the cancer cell targeting and low side effects of drug-loaded composite particles.Conclusion: In this paper,the drug targeting release systems of6MP@ZIF-90,(Ara+6MP)@ZIF-90,(5FU+6MP)@ZIF-90 and MTX@ZIF-90@CS were successfully prepared by a simple and efficient one-pot method.Through a variety of characterization methods,in vitro release experiments and cell activity experiments,the results showed that.The composite drug delivery system based on ZIF-90 showed excellent biocompatibility and p H response targeted release of anticancer drugs.In addition,two anticancer drugs were loaded into ZIF-90 carriers at the same time,and the effect of synchronous targeted drug release was obtained,which provides a new idea for the development of multi-mechanism targeted drug delivery system.The research results of this paper further verify the application value of ZIF-90 as a candidate of new intelligent drug delivery materials,and provide reference and reference for the application research of MOFs materials as a new drug delivery system. |
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