Application Of Gold Oxide Nanocomposite Carrier In The Treatment Of Tumors With Hypoxic Microenvironment

Nowadays,for the treatment of cancer,whether it is for traditional treatment or new treatment methods,the micro-environment of cancer cells especially the hypoxic micro-environment has played a certain role in hindering treatment.In order to over this barrier,we prepared multifunctional nanomaterial.Among these nano materia Is,the materials with oxygen-producing effects are most prominent in improving the hypoxic microenvironment of cancer cells.In addition,a multifunctional nanocarrier is prepared on the basis of a material that generates oxygen function,in combination with other nanomaterials having light,heat,magnetic properties.This paper has conducted some researches on cancer treatment application of several gold oxide nanocomposite drug foading system.The specific content is as follows:In order to overcome the hypoxic microenvironment of cancer cells and improve the therapeutic effect of chemotherapy:Magnetic Fe3O4@SiO2@Au2O3OFeSiAuO)nanoparticles were prepared.Then,anticancer drug DOX was loaded onto the surface.The as-prepared Fe3O4@SiO2@Au2O3 nanoparticles have regular sliape and good dispersion,and the particle size is only 25 nm,which is suitable for biological applications.The composite has a large specific surface area(365.24 m2/g),which is beneficial to the load of anticancer drugs.The synthetic material is superparamagnetic and enables magnetic targeted therapy.Under certain wavelength excitation,Au2O3 will decompose oxygen to make up for the lack of oxygen in cancer cells.After the DOX was loaded,corrparison of release under the light and without illumination indicates that Au2O3 in the sustained release system can release oxygen to promote the release of DOX,and the final release efficiency can reach 67%.At the same time,Fe3O4@SiO2@Au2O3 nanoparticles are not toxic to normal cells(after 48 hours of co-culture with cells,the cell activity is still above 90%).Under the action of light and magnetism,the cancer cell inhibition of Fe3O4@SiO2@Au2O3-DOX was obvious(cancer cell survival rate is be low 10%).In addition,upon the 560 nm light,the concentration of the dissolved oxygen can be remarkably improved from 0.2310.15 ppm to 6.23±0.15 ppm,which indicating that the oxygen-producing function of the prepared material can relieve the hypoxia microenvironment of cancer cell.In vivo experiments also showed that the presence of Au2O3 under light can significantly inhibit the growth of tumors,and ultimately improve the therapeutic effect of chemotherapy.In order to overcome the hypoxic microenvironment of cancer cells and improve the therapeutic effect of photodynamic therapy:(1)MnO2@Au2O3-Ce6 nano-carrier was prepared.The ultra-thin flake MrnO2 provides the conditions for the loading of Au2O3 and Ce6.In addition,the loaded Au2O3 can also produce oxygen under light,so Ce6 can react with more O2 under light,so that it can effectively improve the effect of photodynamic therapy.The synthesized MnO2 is in the form of flakes with irregular morphology,with large area and does not require modification,whose surface is loaded with more Au2O3 particles.Moreover,prepared materials are not toxic to normal cells,the cell activity still reached over 90%after 48 h of co-culture with the cells.And MnO2@Au2O3-Ce6 has obvious inhibition to cancer cells in the light(cancer cell survival rate is below 23%).Dissolved oxygen concentration increased by 1.5 mg/mL during light.In vitro photodynamic experiments also showed that the ability of the material to produce O2 can significantly increase the efficiency of photodynamic therapy.(2)UCNPs@SiO2@Au2O3(UCSiAuO)nanocomposites with oxygen production were synthesized to lade the photosensitizer Ce6.Under near-infrared(NIR)laser light,energy from UCNPs will transfer energy to Au2O3 through the fluorescence resonance energy transfer(FRET)effect,causing Au2O3 to decompose and release O2-When Chtorine6(Ce6)photosensitizer is loaded,under the same illumination,the generated O2 can be directly used to produce reactive oxygen species ROS that are toxic to cancer cells,so as to achieve a higher therapeutic effect under hypoxic conditions.The average particle size of the synthesized nanocarriers is about 78 nm,whose shape is regular and uniform.It has good biocompatibility and stability,and has a large specific surface area(398 m2/g).It has been proved that the oxygen production capacity(dissolved oxygen increased from 0.5 ppm to 6.9 ppm in the light)by solution experiments.In addition,a series of cell experimental assays validated the high-efficiency PDT effect of UCSiAuO-Ce6.The final in vivo photodynamic therapy study can deduce that the oxygen produced is a major factor in promoting the effect.