Preparation And Study Of Transition Metal Nanoparticles For Tumor-based Synergistic Therapy

Cancer is one of the major public problems that seriously threaten human health worldwide.Surgical treatment,chemotherapy and radiotherapy as the three traditional treatment methods,can not really achieve the cure of canceral,though to a certain extent can prolong the survival of cancer patients.In recent years,with the rapid development of nanotechnology in the field of biomedicine,the construction of multifunctional nanomaterials for cancer diagnosis and treatment has become the most active research field.Among them,photothermal therapy and photodynamic therapy based on nanomaterials have shown great potential in cancer treatment with the advantages of non-invasive and high specificity.Transition metal sulfides have been widely used in photothermal therapy due to their excellent photothermal properties.However,the preparation process is complicated or toxic substances are introduced,which requires modification for further application.Photodynamic therapy is an oxygen-dependent treatment,and hypoxia in the tumor microenvironment can weaken the effect of photodynamic therapy.In addition,single photothermal or photodynamic therapies are difficult to achieve the desired therapeutic effect;therefore,combined multimodal therapies have become a hot research topic.To address the above problems and combine with current research trends,this paper synthesizes,based on biomineralization strategy,1)transition metal sulfide nanoparticles with both chemodynamic and photothermal therapeutic effects,and 2)multifunctional nanoenzymes for combined photodynamic-chemodynamic tumor treatment by a simple,green and efficient one-step method.1)Transition metal sulfide nanoparticles:Due to the Localized Surface Plasmon Resonance effect,copper sulfide nanomaterials have a strong near-infrared absorption ability and are thus widely used in photothermal therapy.However,the preparation process generally requires high temperature and pressure,and the reaction conditions are harsh and complicated.In addition,disadvantages such as low photothermal efficiency and poor biocompatibility limit their further biological applications.To overcome these difficulties,silver-doped copper sulfide nanoparticles(BSA-Ag:CuS,BACS)were synthesized based on a biomineralization strategy using bovine albumin as a template and stabilizer.The doping of silver improves the near-infrared light absorption of copper sulfide nanoparticles and enhances their photothermal efficiency.BACS can be used for 1064 nm laser-guided photothermal therapy.The divalent copper ions also have chemodynamic therapeutic effects and can be synergistically treated with photothermal therapy,which has an efficient cancer inhibition performance of 1+1>2.BACS has good material stability,low biotoxicity,good biocompatibility,and efficient tumor suppression ability.The results of in vitro and in vivo experiments suggest that BACS can be used as a promising reagent for cancer therapy.2)Multifunctional nanoenzymes:Based on the tumor microenvironment with high concentration of hydrogen peroxide(H₂O₂),nanomaterials with peroxidase-like(CAT)function are introduced to decompose H₂O₂ to provideO₂,from improving the hypoxic state of the tumor microenvironment to improve the photodynamic therapy effect.In turn,the weakly acidic microenvironment allows peroxidase-like enzyme(POD)to catalyze H₂O₂ to produce efficient reactive oxygen species·OH for chemodynamic therapy.A biomineralization strategy using bovine serum protein as a template and stabilizer was designed and synthesized with a cerium oxide multifunctional nanoenzyme loaded with the photosensitizer Ce6(BSA-CeO₂-Ce6).BCC has efficient CAT performance and can decompose overexpressed H₂O₂ into O₂,enhancing O₂-dependent photodynamic therapy.In addition,it can exert POD at lower p H for chemodynamic therapy.Under the guidance of NIR,BCC possesses photodynamic-chemodynamic synergistic therapeutic properties and exhibits efficient tumor growth inhibition.BCC has good biocompatibility,low biotoxicity.Based on the experimental results,BCC has great potential for application in cancer therapy.