| Cancer has become one of the serious threats to human life.Chemotherapy is the major therapeutic treatment in clinical application,killing cancer cell by chemical drugs.It is difficult for traditional chemical drugs for reaching anti-cancer effect,because some disadvantages are still up in the air,such as high toxicity side effect and low bioavailability.Therefore,it is necessary to construct a reasonable drug delivery system to improve the efficiency of chemotherapy.Based on polymer microspheres,drug delivery system could maintain blood concentration in the working rang by inhalation or oral administration,which provides great potential values in research and developments in cancer treatment.Up to now,a lot of researches have developed numerous stimulation-responsive drug delivery carriers based on polymer drug delivery systems,which depend on differences in cellular environment or external artificially induction,realizing positively release chemical drug and improving cancer treatment efficiency.Among them,adenosine triphosphate(ATP)responsive drug delivery had been considered as an ideal stimulus signal,triggered by different ATP concentration of normal and pathological sites without external stimulation.The MOF with larger specific surface area,stable structure,convenient modification and stimulate-response effect,can be a promising platform for loading and delivering cargoes,such as cancer therapeutic drugs and imaging agents.However,MOF as drug delivery systems still remain some challenges,that it is difficult to maintain the effective concentration of chemical drugs in the blood,leading negative impact on target sites.In this paper,the ATP-responsive drug delivery system was designed.A novel ATPtriggered drug release system based on porous polymer microspheres was prepared by poly(lactic-co-glycolic acid)(PLGA)and ZIF-90 as drug delivery carriers.The triggered release of chemical drug Dox by ATP stimuli was fabricated and evaluated in the vitro.Meanwhile,F(?)rster resonance energy transfer(FRET)between flavin mononucleotide(FMN)and Dox was demonstrated in ZIF-90.The article will start from the following aspects:Firstly,ZIF-90 containing aldehyde group was prepared by one-step method,and then DOX containing amino group and ZIF-90 were covalently combined by a mild Schiff base reaction to obtain Dox@ZIF-90 nanocrystals with high drug loading(69.6 %)and high encapsulation rate(78.9 %).The results of scanning electron microscopy images and hydrodynamics size showed that the size of Dox@ZIF-90 was uniform and had great dispersion.Then,porous microspheres of Dox@ZIF-90@PLGA were prepared by double emulsionsolvent evaporation method.The PLGA with pore structure,facilitated entry of ATP from the external environment and the internal drug release.The absorption spectra of UV-Vis showed the change of drug cumulative release rate under different ATP concentration and release time,which realized the ATP response release and drug slow release.CCK-8 and hemolysis experiments showed that ZIF-90@PLGA porous microspheres had great biocompatibility and low hemolysis rate.Finally,FMN could offer special fluorescence properties on drug delivery carriers,due to the good biocompatibility and high fluorescence intensity.FMN as fluorophore donor and DOX as fluorophore receptor,fluorescence signal enhancement of DOX was achieved by FRET effect.FMN and Dox were adopted to load in ZIF-90 based on simulated calculation.Excited at 490 nm,FMN-Dox@ZIF-90 emitted intense orange fluorescence,demonstrating the formation of FRET molecular pairs in the ZIF-90 nanocrystals.A novel ATP-responsive controlled drug release system based on PLGA porous microspheres is expected to be an effective drug delivery carrier for the treatment of gastric cancer and lung cancer. |
PDF Full Text Request