Preparation Of Paclitaxel Loaded Core-shell Magnetic Mesoporous Silica Nanoparticles And Its Study On Antitumor Activity

The incidence of cancer has been increasing for years as the human’s living environmentcontinues to deteriorate.Currently,cancer is seriously endangering human life and health.Non-surgical treatment of cancer mainly involves chemotherapy and radiation therapy.In cancer treatment,traditional anti-tumor drugs cannot distinguish diseased cells from normal ones so that these drugs will always bring undesired side effects to the body while killing the cancer cells.Moreover,the effect of a single anti-tumor drug is not satisfactory because of the complexity of tumor cells and tissues.However,drug delivery systems targeting tumor tissues will avoid killing the normal cells,leading to low toxicity.In recent years,magnetic mesoporous silica nanoparticles（MMSN）have developed rapidly in the field of biology and medicine as an advantageous drug carrier because of their non-toxicity,good biocompatibility,easily controlled particle size&pore size,and large specific surface area for drug loading.Magnetic nanoparticles as an anti-tumor drug carrier for targeted delivery of drugs to tumor tissues have been attracting more and more attention.In this paper,our research was conducted as follows:firstly,the magnetic nanoparticles withcore-shell structure were synthesized.Secondly,the superparamagnetic Fe₃O₄ nanoparticles with average particle size of 195 nm and zeta potential of-38.1 mV were prepared by solvothermal method using cetyltrimethylammonium bromide（CTAB）as the template and tetraethyl silicate as the silicon source.Magnetic mesoporous silica materials coated with Fe₃O₄ were obtained through the self-assembly of Fe₃O₄in ammonia.The magnetic properties of Fe₃O₄ were investigated by sol-gel method.Pore silica.The resulting magnetic mesoporous silica had an average particle size of 224 nm.Finally,the surface of the magneticFe₃O₄@mSiO₂nanoparticleswithcore-shellstructurewasmodifiedwith3-aminopropyltriethoxysilane（APTES）,activated with EDC/NHS,and reacted with hyaluronic acid（HA）.HA could be conjugated onto the surface of the magnetic mesoporous silica through an amide bond,thereby forming hydrophilic Fe₃O₄@mSiO₂-HA nanoparticles.The antitumor drug paclitaxel（PTX）was loaded onto the nanoparticles.The mechanism of drug loading and release were studied subsequently.MTT assay and laser confocal microscopy were employed to investigate the targeting ability ofthe PTX-Fe₃O₄@mSiO₂-HA nanoparticles and their inhibitory effect on the growth of cancer cells.These results showed that this preparation could obviously kill tumor cells and efficiently deliver drugs to the cells with high expression of CD44 receptor as it had good targeting ability under the receptor-mediated action.In vitro safety evaluation showed that the prepared PTX-Fe₃O₄@mSiO₂-HA formulation hadgood hemocompatibility without any hemolytic reaction.The vascular irritation test results demonstrated that this preparation resulted in no significant pathological changes that could be observed by naked eyes,indicating that it was a safe and reliable formulation without irritation to blood vessels.It can be concluded from all the above results that the Fe₃O₄@mSiO₂-HA prepared in this projectis a good carrier for anti-cancer drugs and would be of potential clinical use in cancer treatment.