Construction Of WS₂ Lipid System And Its Application In The Field Of Drug Delivery And Multiple Combination Therapy For Tumor

Cancer is still a very challenging health problem facing all mankind.The strategies adopted to overcome the defects of traditional treatment mainly include the synthesis of new drugs and the design of new drug carriers to reduce the toxic and side effects of existing anti-cancer drugs.Tungsten disulfide?WS₂?is a graphene oxide-like nanomaterial with high specific surface area and excellent light-to-heat conversion characteristics.However,due to its poor stability under physiological conditions and low biocompatibility,its application in the field of biomedicine is greatly restricted.Therefore,it has become a hot research direction to modify it through physical adsorption and ligand to obtain stable and multifunctional composite materials under physiological conditions.Liposome is a kind of cell membrane material with high biocompatibility and good affinity,which can improve the drug delivery efficiency in the body and reduce the toxic and side effects of the drug.There have been many reports in the literature on the modification of spherical inorganic mesoporous silicon and spherical inorganic gold nanoparticles by liposomes,but there are few research reports on the modification of two-dimensional layered nanomaterials including WS₂.In this project,WS₂ was used as the base material,and liposomes were used for surface modification to construct a stable multifunctional nano platform of the biomimetic lipid system,and to conduct serial characterization and evaluation in vivo and in vitro.The specific research results are as follows:?1?Taking WS₂ as the core,functional modification by doping of magnetic particles and gold nanoparticles,and further using liposomes to modify WS₂,mWS₂,WS₂/Au to improve the stability under physiological conditions.TEM,AFM,XRD,particle size,potential and FTIR were used to characterize the structure.The results showed that WS₂-lipid,mWS₂-lipid,WS₂/Au-lipid had been successfully prepared,and the liposomes were completely adsorbed on the surface of WS₂.The in vitro stability experiments proved that the lipid-modified composite material showed good stability before and after drug loading,and reduced the amount of non-specific protein adsorption.The in vitro drug loading and drug release experiments prove that the synthesized composite material has a high drug loading rate and the drug release shows a significant pH dependence.In addition,the experiments of near-infrared promoting drug release proved that doxorubicin?DOX?showed a significant NIR and pH dual-response release curve.The in vitro cell uptake and cytotoxicity were investigated.The results showed that all materials can be taken up well by the cells and accumulated in the cytoplasm,and the pure carrier has good biocompatibility and almost no toxicity to cancer cells.After loading the drug,it showed a concentration-dependent killing effect on cancer cells.?2?WS₂ doped with magnetic nanoparticles shows good superparamagnetism,can be targeted to tumor tissue under the action of an external magnetic field,and can be used as a contrast agent for MRI imaging in bioimaging field.In addition,the photothermal heating experiments of mWS₂-lipid and WS₂/Au-lipid have verified their excellent near infrared absorption and photothermal conversion characteristics.The results of in vitro cell experiments showed that the cell survival rate of the combined treatment group was significantly lower than that of the single treatment group,which initially showed the advantage of phototherapy chemotherapy combined treatment in cancer treatment.In addition,through the establishment of animal models to investigate the uptake of materials in vivo,the results show that lipid-modified materials are more likely to enter cancer cells,and show a more obvious effect of photothermal heating.Finally,we conducted an in vivo combination therapy study on animal experiments through the WS₂/Au-lipid system,which is the most obvious photothermal ablation.The results showed the same therapeutic effect as in vitro cell experiments,indicating that the WS₂ biomimetic lipid system we constructed exhibited excellent results in multiple combined treatment of cancer.