Construction And Evaluation Of Chemo/phototherapy Integrated Targeting Nanocarriers Based On MOFs

Metal-organic frameworks（MOFs）are characterized by structural customizability,high specific surface area,and functional diversity.Therefore,nano-drug delivery systems based on MOFs show great potential in the biomedical field.At present,chemotherapy is the main method for the treatment of cancer.However,serious side effects,drug resistance and other problems affect the treatment effect.Synergistic photodynamic and photothermal treatment methods can effectively improve the anti-cancer effect.This emerging combination therapy has also attracted widespread attention.In view of this,this subject designed a targeted nano-drug delivery system based on MOFs to realize the integration of chemotherapy and multiple therapies.Carry out the following work:（1）The DI@Ui O-66-TK-PEG-F3 targeted nano-drug delivery system was synthesized and characterized.A p H-sensitive Ui O-66-NH₂ carrier core was prepared,and the chemotherapeutic drug doxorubicin（DOX）and photosensitizer（ICG）were co-encapsulated in the carrier core by physical adsorption,providing a strategy of chemo-phototherapy for anti-tumor.The surface of the drug-loaded core DI@Ui O-66-NH₂ was modified with the multifunctional polymer TK-PEG-F3,and the polymer layer can improve the stability of the drug-loaded core,reduce premature drug release while increasing the biocompatibility and active targeting of nanocarriers.¹H-NMR,¹³C-NMR,FT-IR,UV,Zeta,XRD and other characterization methods were used to verify the successful preparation of the targeted nano-drug delivery system DI@Ui O-66-TK-PEG-F3.（2）To explore the properties of DI@Ui O-66-TK-PEG-F3 targeted nano-drug delivery system.The particle size of the nanocarrier Ui O-66-TK-PEG-F3 in the dry state was 70nm as observed by transmission electron microscopy（TEM）,and the morphology and size were uniform.The average hydrated particle size measured by dynamic light scattering（DLS）was 225 nm,which indicated that its suitable particle size could be used in nano-drug delivery systems.Thermogravimetric analyzer（TGA）and nitrogen adsorption-desorption analyzer（BET）test results verified the thermal stability and high specific surface area and pore value of the nano-drug carrier.The drug loadings of DOX and ICG in DI@Ui O-66-TK-PEG-F3 were detected to be 15.4%and 6.17%,respectively.In vitro generation of reactive oxygen species and photothermal properties,the results show the generation of reactive oxygen species and better photothermal efficiency.The in vitro drug release experiments proved that the DI@Ui O-66-TK-PEG-F3 nano-drug delivery system has the ability to release drugs in response to stimuli,realize the controllable drug delivery,improve the therapeutic effect,and reduce the toxic and side effects caused by off-target drug delivery.（3）The biological evaluation of the DI@Ui O-66-TK-PEG-F3 targeted nano-drug delivery system was performed at the cellular level in vitro.The results of in vitro cytotoxicity experiments and uptake experiments showed that the DI@Ui O-66-TK-PEG-F3 targeted nano-drug delivery system has good biosafety.The decreased cell viability and the production of reactive oxygen species after irradiation with 808 nm near-infrared light indicate that the integration of chemotherapy and phototherapy has enhanced tumor cell killing effect.In addition,it was also confirmed that the F3 polypeptide linked to the targeted nanodrug carrier could mediate the uptake of the nanodrug carrier by MDA-MB-231 cells.By specifically binding to the overexpressed nucleolin on the cell surface,the nanocarrier had tumor targeting.