Preparation Of Multifunctional Nanomaterials Based On NaYF4:Yb,Er And Research On Anti-tumor Performance

In recent years,rare earth up-conversion nano-drug carrier systems have shown unique advantages in the field of tumor multimodal imaging and cancer combined therapy.Especially lanthanide-doped up-conversion nanomaterials can convert near-infrared light into visible light or ultraviolet light through a multiphoton process,and have the characteristics of weak autofluorescence,high stability,and high signal-to-noise ratio.It has a wide range of applications in the field of biomedicine.In addition,near-infrared light has the characteristics of strong tissue penetration and high biological safety,which is more conducive to in vivo optical imaging and tumor treatment.Based on the above considerations,this paper uses the high temperature solvothermal method to prepare Rare Earth Upconverting nanoparticles（UCNPs）,and then uses cucurbituril[7]（Cucurbituril[7],CB[7]）with a macrocyclic structure for surface modification,Carrying or bonding anti-tumor drugs.The imaging capabilities of the materials,biocompatibility,drug loading and release,and tumor suppression effects have been studied in detail.The specific content is summarized as follows:（1）Design and synthesize a drug delivery system with Na YF₄:Yb³⁺,Er³⁺@CB（UCNPs@CB）as carriers.First,Na YF₄:Yb³⁺,Er³⁺nanoparticles encapsulated by oleic acid were synthesized by high-temperature solvothermal method,and then CB was used to replace the oleic acid on the surface of UCNPs by a ligand exchange method to synthesize water-soluble nanoparticles.The obtained material emits bright green light under the excitation of 980 nm near-infrared light.The broad-spectrum anticancer drug Doxorubicin（DOX）is used as a model drug to evaluate drug loading and tumor cell suppression effects.Due to the macrocyclic structure of CB,Fourier Transform infrared spectroscopy（FTIR）and UV-Vis Absorption Spectroscopy（UV-Vis）show that DOX has a good load;MTT results show that the load is DOX The latter UCNPs@CB-DOX has a significant inhibitory effect on the proliferation of SK-OV-3 and A2780 cells;the single-drug DOX and UCNPs@CB-DOX on the apoptosis results of A2780 cells show that with the increase of drug concentration,the cell apoptosis The death rate was also significantly increased;mitochondrial membrane potential results showed that compared with the UCNPs@CB group alone,DOX and UCNPs@CB-DOX treated A2780 cells for 24 h,the mitochondrial membrane potential decreased significantly;endocytosis experiments also showed that UCNPs@CB-The endocytosis efficiency of DOX is lower than that of the single-drug DOX group.This is attributed to the fact that DOX enters cells through free diffusion,while nano-drugs usually enter cells through endocytosis;in the Upconversion luminescence（UCL）imaging experiment,UCNPs@CB-DOX was injected into the tumor site of mice,and the in vivo imaging results showed obvious UCL fluorescence signals,which verified the upconversion fluorescence imaging effect of the drug delivery vector.Therefore,the good biological safety demonstrated by this material has a wide range of applications in cancer treatment and imaging.（2）Design and synthesize a dual-drug delivery system of zoledronic acid（ZOL）and cisplatin（Pt）with Na YF₄:Yb³⁺,Er³⁺@CB（UCNPs@CB）as carriers（UCNPs@CB-ZOL-Pt）.Through FTIR and nuclear magnetic resonance（Nuclear magnetic resonance,NMR）proved the successful loading of ZOL and Pt;MTT results show that single-drug Pt has a significant inhibitory effect on 4T1,A549,A2780,SK-OV-3 cells,ZOL only It can inhibit the proliferation of 4T1 cells;the synthetic UCNPs@CB-ZOL has obvious toxic effect on 4T1 cells,which is consistent with the analysis results of single-agent ZOL on 4T1 cytotoxicity;different concentrations of UCNPs@CB-ZOL-Pt nanomaterials after treatment of SK-OV-3 and 4T1 cells,cell viability decreased slowly with the increase of drug concentration;Apoptosis also showed the same trend;UCNPs@CB-ZOL and UCNPs@CB-ZOL-Pt acted on 4T1cells for 24 h After that,the mitochondrial membrane potential decreased significantly;in the in vivo anti-tumor experiment,the UCNPs@CB-ZOL-Pt group significantly inhibited tumor growth,combined with PD-1 inhibitors,the effect of inhibiting tumor growth was more significant;in vivo imaging results were also It showed obvious UCL fluorescence signal,reflecting that the synthesized UCNPs@CB-ZOL-Pt did not weaken the imaging effect due to the multi-layer drug loading.Therefore,the dual-drug delivery vector has potential application value in cancer diagnosis and treatment.