Construction Of Nanoscale Drug Delivery Systems Based On Biological Metal-Organic Complex

Recently,metal-organic complexes(MOCs)have attracted increasing attention in the construction of responsive nanodrugs for cancer treatment.However,conventional MOCs materials are usually synthesized from toxic metals or organic ligands with low biocompatibility and are not responsive to the tumor microenvironment.On the other hand,folic acid and its derivatives play an important role in the construction of targeted nano-drug delivery systems due to their ability to bind specifically to folic acid receptors on the surface of many cancer cells.Based on this,in chapter 2,a novel biomaterial bioMOC-Zn(Cys)was constructed with endogenous metal ion Zn2+ as the metal node and the biomolecular L-cy stine(Cys)as the organic ligand.And DOX@bioMOC-Zn(Cys),a reduction-responsive nano drug,was prepared with DOX,an anticancer drug,loaded with it.Our study has shown that DOX@bioMOC-Zn(Cys)meets the EPR effect profile and particle size requirements.And in vitro experiments,DOX@bioMOC-Zn(Cys)nano-drugs show responsive release behavior to reduced glutathione(GSH).Cell experiments showed that the uptake rate of DOX@bioMOC-Zn(Cys)in A549 cells was much higher than that of free DOX,and showed strong anticancer toxicity,and the biocompatibility of bioMOC-Zn(Cys)materials was good.Animal experiments have shown that DOX@bioMOC-Zn(Cys)nano-drugs have stronger anticancer effects than free DOX.Further,based on the preparation of DOX@bioMOC-Zn(Cys)nano-drugs,folic acid was used as an active targeting modifier in Chapter 3 to modify folic acid onto the surface of nano-drug carriers,and a nano-drug delivery system DOX@FA-bioMOC-Zn(Cys)with reductive responsiveness and active targeting functions was constructed.Studies have shown that the morphology and particle size of DOX@FA-bioMOC-Zn(Cys)still meet the requirements of nano-drugs,and it has a higher intake and fatality rate for HeLa cells than DOX@bioMOC-Zn(Cys)and free DOX,which confirms the synergistic effect of reductive response binding active targeting on improving the therapeutic effect of nano-drugs.In this paper,two kinds of MOCs based nano-drug delivery systems have good biocompatibility,high drug load rate and enhanced tumor treatment effect,which are expected to provide technical reference for the development and application of new nano-drugs.