Fabrication Of ROS-Responsive Silicon Drug Delivery System And Its Anti-tumor Application

With the increase of the average life expectancy in the world,the deterioration of the living environment and the difficulty of curing cancer,cancer is increasingly becoming a damage to the health and safety of human life.The development of nanotechnology has provided strong support for cancer diagnosis and treatment,among them,silicon nanoparticles have been widely studied for their advantages such as good biocompatibility,abundant surface chemical sites,and pore channels for easy storage of guest molecules.Silicon nanoparticles with responsive properties,which are developed for the special microenvironment of cancer cells compared to normal cells,have become research hotspots due to their intelligent,fast and safe drug release behavior.Based on the good biochemical properties of silicon nanoparticles,combined with the special microenvironment of cancer cells,this article has developed three nano-drug delivery systems with intelligent responsibility and anti-cancer properties.The main results are as follows:（1）Based on the significantly higher ROS concentration of cancer cells compared to normal cells,ROS-responsive composite nano-drug system（MSNs-TK-m PEG）was designed to carry model drugs Doxorubicin（DOX）and fight cancer.Mesoporous silica nanoparticles（MSNs）with large specific surface area,large pore volume,uniform size and a particle size of less than 200 nm were prepared by the classic soft template method.Using the rich surface chemical sites of MSNs,a modified m PEG with ROS-responsive properties was grafted to obtain MSNs-TK-m PEG for loading the anticancer drug DOX.The nanostructures and morphology of the nanoparticles were characterized by Fourier transform infrared spectroscopy,transmission electron microscopy,scanning electron microscopy,N₂ adsorption/desorption,dynamic light scattering,and thermogravimetric analysis.we comprehensively evaluated the drug release performance of the DOX@MSNs-TK-m PEG system in vitro,the cytotoxicity of the nanosystem,and the anti-cancer performance in vitro.（2）In this work,a novel thioacetal bridged silsesquioxane（BTMPTA）was synthesized,and as one of the precursors,mesoporous organosilica nanoparticles（MONs）with reactive oxygen species（ROS）responsive properties were synthesized,hydrophilic macromolecular polyethylene glycol grafted on the surface,loaded with DOX to form a composite drug delivery system（DOX@MONs-SA-m PEG）for preliminary performance testing.The nanostructures and morphology of the nanoparticles were characterized by Fourier transform infrared spectroscopy,transmission electron microscopy,scanning electron microscopy,N₂ adsorption/desorption,dynamic light scattering,and thermogravimetric analysis.In vitro ROS responsive degradation experiments intuitively demonstrated the responsive degradation ability of MONs with BTMPTA as a precursor.In vitro drug release experiments showed that DOX@MONs-SA-m PEG had a ROS-responsive drug release effect.（3）Based on the"chemical homology"mechanism and"ammonia-assisted selective etching"strategy,hollow mesoporous organosilica nanoparticles（HMONs）with ROS responsive properties were synthesized,and then the surface of the nanoparticles was coated with p H-responsive polydopamine（PDA）biofilm and grafted amino-terminated methoxypolyethylene glycol（m PEG-NH₂）to form a dual-responsive smart drug system（HMONs@PDA-m PEG）to deliver Doxorubicin（DOX）.In vitro degradation experiments in a simulated ROS microenvironment showed that thioacetal-bridged HMONs are responsive to ROS.In vitro drug release profiles showed a synergistically p H-dependent and ROS-responsive drug release effect.MTT assay toward A549 cells demonstrated that drug carriers had a biocompatibility,and DOX-loaded nanoparticles presented a concentration-dependent and time-dependent cell growth inhibition effect.In summary,the novel ROS-responsive HMONs@PDA-m PEG had a promising application as a smart drug delivery system in biomedical field.