| Cancer is a malignant disease which is difficult to treat in modern society,it has been a major obstacle to the development of public health and the improvement of people’s living standard because of its increasing incidence rate and mortality rate.The emergence and development of nanomedical carriers bring opportunities and hopes to solve the problems in tumor treatment and improve the survival of patients.It has become a hot topic in the field of nanomedicine research to apply nanomedical materials to the traditional means of tumor treatment,to give full play to the advantages of nanomaterials in size and physicochemical properties,and to broaden the treatment ideas and ways.As the latest kind of ordered porous solid Metal-Organic Frameworks(MOFs)materials have many kinds and different functions,which have great potential to develop into nano drug carriers.However,at present,the research of nano Metal-Organic Frameworks(n MOFs)as drug carrier is not comprehensive,most of the research is still focused on the granular n MOFs and the embedded drug carrier,which makes it difficult to further improve the drug loading rate and release effect.It is of great significance and research value to develop a new type of n MOFs,regulate its morphology,structure and drug loading level,and explore its biological effects,for improve the effect of tumor treatment and optimize the treatment plan.In order to achieve this goal,we designed and constructed DOX@Cu-TCPP,an acid responsive nanosheet with metalorganic frameworks drug delivery system combined with photodynamic therapy.The system is based on the MOF nanosheet which is composed of photosensitive tetracarboxyporphyrin derivative and copper ion as drug carrier platform,and adsorbs adriamycin through π-π stacking,so as to achieve the purpose of photodynamic combined chemotherapy in the treatment of tumor.Photodynamic therapy can avoid the drug resistance of tumor cells and interfere with the drug resistance mechanism of tumor cells by destroying the balance of oxidative stress in tumor cells,so as to improve the chemotherapy effect;meanwhile,in the process of chemotherapy,nano materials can reduce the cell reduction environment and improve the sensitivity and therapeutic effect of photodynamic therapy by removing intracellular reduced glutathione,so photodynamic / chemotherapy combination therapy has significant advantages.In order to verify this assumption,we used transmission electron microscopy,atomic force microscopyand dynamic light scattering to detect the morphology and size of nanomaterials;X-ray diffraction and X-ray photoelectron spectroscopy to characterize the structural characteristics;zeta potential,Fourier near infrared spectroscopy and ultraviolet spectrophotometer to analyze the stability of materials and the loading of adriamycin;in vitro release experiments were carried out to verify the acid responsive release behavior;detection of GSH consumption and ROS generation in solution.In addition,We use 4T1 cells as the model to investigate the antitumor efficiency of the nanodrug delivery system combined with photodynamic at the cellular level by detecting cell activity(CCK-8),cell uptake materials and intracellular ROS production and cell apoptosis(confocal microscope and flow cytometry instrument);In vivo,the animal model was constructed to observe the animal survival and tumor growth.Explored the biological safety and anti-tumor effect of nanodrug delivery system combined with photodynamic in vivo.The results show that the DOX@Cu-TCPP drug delivery system constructed by us has the characteristics of appropriate size,stable dispersion,the ability of ROS release in response to near-infrared light and drug release in response to intracellular low p H.It shows good biocompatibility and excellent antitumor effect in vitro and in vivo.This study opened up a new way for MOF nanosheet to be used in tumor treatment,and provided a supporting basis for photodynamic therapy. |
PDF Full Text Request