Preparation And Antitumor Mechanism Of Nanosystems With Mesoporous Silica As Carrier

As we all know,cancer is now one of the main dangers that threaten the safety of human life.The side effects of traditional cancer treatment seriously affect people’s lives.The development of new anti-tumor drugs is an urgent task.Two nanocomposites based on mesoporous silica were synthesized.First,we loaded the ferroferric oxide(PA)with non-toxic mesoporous silica and modified L-ascorbyl palmitate(PA)on the surface to obtain a magnetic nano-particle Fe3O4@mSiO2-PA.SEM,TEM,IR and other methods show that Fe3O4@mSiO2-PA has excellent magnetic properti es and dispersibility,and the particle size is uniform.MTT experiments,flow cytometry,sectioning,and in vivo experiments show that Fe3O4@mSiO2-PA inhibits tumor proliferation better than Fe3O4@mSiO2.It is speculated that PA may produce hydrogen peroxide in the tumor environment,and further Fenton reaction between Fe2O4 and hydrogen peroxide produces excessive reactive oxygen species ROS,which induces apoptosis of tumor cells.We have synthesized another mesoporous silica composite Ru@mSiO2-PA with a ruthenium complex Ru(bpy)3C12 as the core.SEM,TEM,IR,etc.indicate that the particle size of the composite Ru@mSiO2-PA is about 50 nm and the dispersion is good,and it has strong fluorescence characteristics.The growth of cells may be due to the Fenton reaction of Ru(bpy)3C12 in mesoporous silica and H2O2 produced by PA in the tumor environment,which generates a large amount of ROS and causes tumor cell apoptosis.We further validated the anti-tumor mechanism of Ru@mSiO2-PA.The results of western blotting showed that Ru@mSiO2-PA could activate the MAPKs signaling pathway in a dosedependent manner,and inhibited the PI3K/AKT signaling pathway in a dose-dependent manner.It was further shown that the inhibition of tumor cell growth by Ru@mSiO2-PA is MAPKs and PI3/AKT dependent.In addition,Ru@mSiO2-PA induced ROS production in a time-dependent manner,and induced DNA damage in a dose-dependent manner,which was characterized by phosphorylation activation of DNA damage marker proteins;however,ROS clearance significantly inhibited MAPKs signaling pathway Activation,inhibition of PI3K/AKT signaling pathway inactivation,attenuation of DNA damage,further attenuated the growth inhibition of Ru@mSiO2-PA on cells,indicating that Ru@mSiO2-PA inhibits tumor cell growth is ROS-dependent.