Construction And Stimuli-Responsive Controlled Release Of Nanoscale Metal-Organic Framework Delivery Systems Loaded With Double Drugs

Nanomedicine is an emerging research field which refers to the application of nanotechnology in medicine,while drug delivery systems dominate nanomedicine research.Drug delivery systems have many advantages over traditional drug therapy,including improved therapeutic efficiency,reduced toxicity,and targeted delivery.At present,most researches on drug delivery systems are focused on cancer therapy,and many stimuli responsive drug delivery systems can be designed according to the tumor microenvironment.External stimuli responsive drug delivery systems are developed as well.Metal-organic framework is a new kind of drug carrier,which has great potential in drug delivery systems due to its controllable composition and structure,high porosity,simple surface modification,and good biodegradability.Combination drug therapy which refers to the simultaneous use of two or more drugs for treatment can not only enhance therapeutic efficacy and reduce side effects,but also reduce drug resistance.Based on the above strategies,a ZIF-8 gated nanoscale metal-organic framework drug delivery system is designed,and the research work of this paper is divided into two parts:1.A ZIF-8 gated UiO-67 delivery system loaded with double drugs is constructed.UiO67 nanoparticles are used as drug carriers,meanwhile rhodamine B(RhB)and 9aminoacridine(9AA)are used as model drugs.Native double-stranded DNA is bound to the surface of UiO-67 nanoparticles through multivalent chelating interactions with ZrⅣ to encapsulate rhodamine B,and 9-aminoacridine is combined with DNA by intercalation and electrostatic interactions for the loading of double drugs.The UiO-67-RhB@DNA-9AA dual drug delivery system can release the two drugs simultaneously under the conditions of phosphates,DNA endonuclease,and thermal stimulation.After further coated with ZIF-8,the stability of UiO-67-RhB@DNA-9AA@ZIF dual drug delivery system is significantly improved,and the system is able to resist phosphates and DNA enzymes.Simultaneous drug release can be triggered by weak acid and phosphates to realize combination drug therapy.2.A ZIF-8 gated CuS@UiO-67 delivery system loaded with double drugs is constructed.Small size CuS nanoparticles with good photothermal performance are embedded in UiO-67 nanoparticles to synthesize CuS@UiO-67 nanoparticles.Similar method is used to construct the CuS@UiO-67-RhB@DNA-9AA@ZIF dual drug delivery system.Two drugs can be released simultaneously under the condition of weak acid and phosphates,and near-infrared(NIR)light can accelerate the release of drugs.The dual drug delivery system has combined photothermal therapy with combination drug therapy to further improve the therapeutic effect which hold promise for cancer therapy.