Construction And Anti-tumor Research Of Biomimetic ZIF-8 Nano-drug Delivery Systems

At present,breast cancer has become the cancer with the highest incidence in the world,seriously threatening the physical and mental health of women,while traditional treatment methods have poor prognosis,serious side effects,and are prone to recurrence and metastasis.Photodynamic therapy(PDT),as an emerging non-invasive treatment modality,has been widely used in the treatment of various cancers.However,tumor immune escape is one of the important reasons for the insufficient efficacy of PDT.Among them,Indoleamine-2,3 dioxygenase(IDO)inhibits T cell immune response by consuming tryptophan and accumulating canine urine,thus leading to tumor immune escape.Therefore,the development of a new nano-drug delivery system with both photodynamic efficacy and IDO pathway inhibition has important research value for enhancing anti-tumor efficacy.In this study,we designed a erythrocyte membrane coated ZIF-8 nano drug delivery system co-containing photosensitizer Ce6 and IDO inhibitor 1-MT,combining the advantages of ZIF-8 with adjustable pore size,high drug loading,p H-responsive drug release and good biocompatibility of erythrocyte membrane,which has achieved the following research results:1.ZIF-8 nano drug delivery system was first synthesized by one-pot method,and co-extruded with erythrocyte membrane vesicles ultrasonically to obtain biomimetic ZIF-8 nano-drug-loading system(ZIF-8-Ce6-IDOi@e M).And its successful synthesis was verified by X-ray diffractometer(XRD),Thermogravimetric Analysis(TGA),Zeta potential,ultraviolet(UV),Fourier Transform Infrared Spectroscopy(FTIR)and other means.2.The results of DLS,SEM and TEM showed that the nanoparticles were spherical in shape,with a particle size of ～150 nm.The drug loadings of 1-MT and Ce6 measured by UV were 6.7% and 12.2%,respectively.The drug release results showed that the drug delivery system had an acid-responsive drug release function,and the drug release rates of Ce6 and 1-MT were 43.6% and 36.9%,respectively,in the p H 5.5 environment.In vitro ROS experiments showed PDT therapeutic potential.3.The anti-tumor effect in vitro was investigated by cell experiments,and the results showed that:(1)Compared with free Ce6,ZIF-8-Ce6-IDOi@e M nanoparticles were easily uptake by 4T1 cells,with better PDT efficacy.(2)Compared with uncoated nanoparticles,ZIF-8-Ce6-IDOi@e M nanoparticles can reduce phagocytosis by macrophages,and reduce immunogenicity.(3)It can produce ROS under 660 nm laser irradiation,with good anti-tumor effect,and low toxicity and good biosafety in the absence of light.(4)It has the effect of inhibiting the catalytic activity of IDO.In conclusion,the bionic ZIF-8 nano drug delivery system constructed in this study has good biosafety and high drug loading capacity,can passively target tumors to achieve p H-responsive drug release,and can give full play to the efficacy of PDT and IDO pathway inhibition,enhance anti-tumor effect.It provides a new safe and efficient way for the treatment of breast cancer.