Preparation And Characterization Of Multifunctional Bismuth-Based Nanoparticles And Their Application In Tumor Imaging And Treatment

The annual death toll from cancer exceeds 10 million,and the death rate from cancer is increasing year by year,which seriously threatens human health.The current treatment methods for cancer mainly include:surgery,radiotherapy,chemotherapy and molecular targeted therapy.However,the curative effect of these traditional treatment methods cannot reach the clinical expected standard and ideal curative effect.In recent years,nanotechnology and nanomedicine have developed rapidly and are expected to become a new treatment strategy to improve the efficacy of cancer.The new multifunctional nanomaterials that integrate diagnostic and therapeutic functions have become a hot research field in nanomedicine.Bismuth is a heavy metal element with stable chemical properties and low toxicity.Studies have shown that bismuth has good X-ray attenuation properties,and bismuthbased nanoparticles are considered to be an ideal CT/PA imaging contrast agent,and have a good combined effect of radiotherapy and photothermal therapy.Bi-based nanomaterials are showing good and broad application prospects in cancer diagnosis and treatment,but so far,there are few researches on multifunctional Bi-based nanomaterials integrating diagnosis and treatment.This study aims to develop a new type of bismuth-based nanomaterial,explore its application in vivo and in vitro CT imaging,photoacoustic imaging,photothermal imaging,and tumor photothermal and photodynamic therapy,and initially evaluate its biological safety,and explore its use as an integrated multifunctional nano platform for tumor diagnosis and treatment,thus provides new ideas and strategies for tumor diagnosis and treatment.The specific research content includes the following two parts:(1)A new type of bismuth-based nanoparticle BiF3:Ln@PVP was successfully prepared by a simple hydrothermal method,and its performance was characterized by transmission electron microscopy,EDS,X-ray diffraction energy spectrum,and ultraviolet absorption spectrum.The results showed that the nano-particle BiF3:Ln@PVP was approximately burr spherical,with an average particle size of about 380 nm.The study found that BiF3:Ln@PVP nanoparticles showed good CT imaging effects in vitro.Under the same dose conditions,the CT imaging effect was better than that of the clinical contrast agent iohexol.BiF3:Ln@PVP nanoparticles displayed good CT imaging effect in tumor tissue and the gastrointestinal tract.BiF3:Ln@PVP nanoparticles did not show obvious cytotoxicity and tissue toxicity in vivo and in vitro toxicity experiments.(2)A new type of nanoparticle Bi-Ag@PVP was successfully prepared by solvothermal method,and its performance was characterized by transmission electron microscopy,EDS,X-ray diffraction energy spectrum,ultraviolet absorption spectrum,etc.The results showed that the appearance of the nano-particle Bi-Ag@PVP was approximately burr spherical,and the average particle size was about 272nm.The nanoparticles have good CT and PA imaging effects both in vivo and in vitro,and the CT imaging effect was better than that of the clinical contrast agent iohexol.BiAg@PVP nanoparticles produced obvious photothermal effects after being irradiated with 808nm wavelength,and induced reactive oxygen species in tumor cells.The tumor-bearing nude mouse model shows that Bi-Ag@PVP nanoparticles can play a good anti-tumor effect through the PDT/PTT synergistic effect after illumination.Further research found that Bi-Ag@PVP Nano Granules can effectively induce tumor cell apoptosis after illumination,and the mitochondrial apoptotic pathway may be its main way to induce tumor cell apoptosis.In addition,the study found that Bi-Ag@P VP nanoparticles have no obvious cytotoxicity and tissue toxicity.In summary,the study prepared BiF3:Ln@PVP and Bi-Ag@PVP two new types of bismuth-based nanoparticles,both of which had good CT imaging effects,and the CT imaging performance was better than that of the clinical contrast agent iohexol.Among them,Bi-Ag@PVP had good CT and PA imaging capabilities and significant PTT and PDT effects.It is expected to realize CT/PA multimodal imaging-guided PDT/PTT cooperative tumor treatment through further research,and provide integrated diagnosis for malignant tumors The new nano-platform integrated with treatment provides new strategies and lays a theoretical foundation for tumor diagnosis and treatment.