The Research About The Synthesis And Hypoxic Tumor Therapy Of Two Copper-selenium-based Core-shell Nanoparticles

Integration of various therapeutic modes and novel hypoxic therapy are two emerging aspects in the current anti-cancer field.Compared with the traditional single therapeutic mode,multifunctional therapeutic modes improve therapeutic efficiency and reduce side effects obviously during the whole treatment.The limitation of the hypoxic tumor environment on the effect of photodynamic therapy has also led scientists to start exploring more hypoxic therapy methods.Based on this,we designed multifunctional therapeutic systems combining photothermal therapy,the newly defined chemodynamic therapy and 2,2'-azobis[2-?2-imidazolin-2-yl?propane]dihydrochloride/doxorubicin-based hypoxic therapy ingeniously,which can take effect well in hypoxic tumor environments.The experimental results show that the constructed copper-selenium-based core-shell nanomaterials can effectively kill tumor cells,which is consistent with the theoretical expectations.And this practice successfully realizes the process that the rational theory guides the reality.The following contents are the main research work of this paper:The CuFeSe₂-based heterojunction was controllably constructed by the coating of metal-organic framework MIL-100?Fe?layer by layer,and the large mesoporous cavities were subsequently filled with the functional material AIPH and phase change material tetradecanol to achieve higher drug loading and controlled heat release of radicals.When irradiated by a single 808 nm laser,the photothermal agent of CuFeSe₂ plays a significant role of the initiating switch in the whole nanoplatform,whose hyperthermia not only realizes fundamental photothermal therapy but also promotes greatly the Fenton reaction of MIL-100?Fe?shell for oxidative hydroxyl radicals production and the generation of toxic AIPH radicals while melting tetradecanol.Besides,on account of the effective attenuation for X-rays of CuFeSe₂,the nanoplatform was also certified to be a superior diagnosis agent for computed tomography imaging.In order to make sure the basic composition and structural information of the material,we first characterized the phase,morphology,functional groups and contained elements by XPS,TEM,FT-IR and XPS.Then,we conducted a series of in vitro cell experiments including toxicity,staining,phagocytosis experiments and in vivo mouse experiments to further explore the biocompatibility and antitumor properties of the materials.As expected,superior performance results indicate that the CuFeSe₂@MIL-100?Fe?-AIPH nanoplatform is expected to play an effective role in the field of hypoxic tumor treatment.Cu_2-xSe nanoparticles with a uniform morphology were synthesized by the high-temperature solvent injection method.After modified by polyvinylpyrrolidone,nanoparticles were converted to water solubility and then coated with metal-organic framework MIL-100?Fe?by one-step solution method.Finally,the large surface area and porous structure of MIL-100?Fe?shells are utilized to load enough antitumor drugs doxorubicin?DOX?.Cu_2-xSe nanoparticle,as an excellent photothermal agent,can be irradiated by the 1064 nm light source with deep tissue penetration depth and low signal-to-noise ratio and takes effect.At the same time,the heat generated by the nanoparticles greatly improved the chemodynamic effect of MIL-100?Fe?and promoted the release process of the anticancer drug doxorubicin.It is worth mentioning that the system can take effect efficiently under the double stimulation of photothermal effect and the acidic pH in tumor microenvironment.In addition,the high permeability and retention effect of the tumor microenvironment enables the nanomaterials to aggregate at tumor sites to take effect,which greatly relieves the damage of the materials to normal tissues.Similarly,we first determined the basic composition information of the synthetic material through several tests to ensure the successful construction of the system in each step;and then we carried out corresponding experiments to test the photothermal and anti-cancer performance of the material.The results prove that the constructed nanoplatform can achieve the synergistic effects of three hypoxic tumor treatment strategies including photothermal therapy,thermally promoted chemodynamic therapy and chemotherapy,and has great potential applications in the field of anti-cancer.