The Synthesis And Safety Evaluation Of Multifunctional Janus-Magnetic Mesoporous Silica Nanocarrier

Nano-material is a new class of materials that are rapidly developing in today's materials field.Their unique properties of physic,chemistry,electricity,magnetism and optics make them useful in the fields of information,biotechnology,energy,environment,and advanced manufacturing technology.Recently,the combination of nanotechnology and medicine has drawn more and more attention.Especially in the cancer research,nanotechnology presents great potential and application prospects.Magnetic-mesoporous silica nanoparticles?M-MSN?as a novel inorganic composite nanomaterials,possessed excellent properties such as nanoscale,magnetic responsiveness,surface functionalization modification which are utilized in drug targeting transport,imaging,and magnetic hyperthermia.Janus magnetic mesoporous silica nanoparticles?J-M-MSN?are asymmetric rod-shaped magnetic mesoporous nanoparticles,compared with conventional spherical magnetic mesoporous silica nanoparticles.They have larger specific surface area and stronger magnetic properties,is expected to be used as a multifunctional nanocarrier for the diagnosis and treatment of tumors.In order to construct a novel multifunctional nanocarrier system,we still need to further functionalize the nanoparticles to achieve functions for imaging and targeting delivery.In this project,based on Janus-type magnetic-mesoporous silica nanoparticles?J-M-MSN?,the tumor-targeting group and fluorescent imaging group will be modified on the surface to enable it to have active tumor targeting,drug delivery and Real-time monitoring of drug treatment processes and other multiple performance.Moreover,we should further verify the safety of the synthesized multifunctional nanocarrier,this project will make a comprehensive evaluation of the in vivo and in vitro safety of the nanoparticles,and take a solid step for its real biological application.PurposeJanus-magnetic mesoporous silica nanoparticles?J-M-MSN?were synthesized,and hyaluronic acid coupled with quantum dots was modified on the surface of the nanoparticles to prepare a novel multifunctional nano-carrier system,which was capable of drug loading,liver cancer targeting and imaging.The multifunctional nanocarrier is investigated in cell experiments and animal experiments,the in vitro safety of the multi-functional nanocarrier is tested,and the acute toxicity and long-term toxicity effects of the multi-functional nanocarrier are discussed,so that the bio-safety of the multifunctional nanocarrier is evaluated,providing theoretical support for the biological application of the multifunctional carrier.Research contentsThe size and shape of J-M-MSN was detected by transmission electron microscope,scanning electron microscope,zeta potential measuring instrument,fluorescence spectrophotometer,laser scanning confocal microscope.The effect of multifunctional nanocarrier on the cellular activity of different normal cell lines and tumor cell lines was detected by SRB assay.Hematology and blood biochemical indexes were examined.HE staining and prussian blue staining of organ slices in acute toxicity and long-term toxicity experiments were analyzed to evaluate bio-safety.Results1.The Fe₃O₄ nanoparticles were prepared by high temperature hydrolysis method,and Janus-magnetic mesoporous silica nanoparticles were synthesized by the method of non-controlled nuclear growth,and the results of characterization and identification showed that they are about 200 to 300 nm long and 100 to 200 nm wide,have a good dispersion in water,and the mesoporous properties were in good agreement with the further requirements.2.The synthesis of multifunctional nanocarrier system?J-M-MSN/HA-QD?was identified by fluorescence spectrophotometer.The results showed that the Janus-magnetic mesoporous surface successfully modified the hyaluronic acid?HA-QD?coupled with quantum dots.3.The cell endocytosis of multifunctional nanocarrier system with HL7702,HepG2 cells was detected by laser scanning confocal microscopy.The results showed that the multifunctional nanocarrier system has the relative higher endocytosis ability in the HepG2 group comparing with HL7702,indicating that J-M-MSN/HA-QD possesses targeting delivery ability for liver cancer.4.The effect of multifunctional nanocarrier system?J-M-MSN/HA-QD?on cell viability was detected on different normal cell lines and tumor cell lines by SRB assay.The results showed that the J-M-MSN/HA-QD was almost nontoxic to normal cells and could be used as a drug carrier for further use.5.The multifunctional nanocarrier system?J-M-MSN/HA-QD?was investigated in acute toxicity and long-term toxicity in ICR mice.The results showed that the LD₅₀of the nanoparticles was 349.2 mg/kg in mice.By using tissue slice technique,HE staining method and Prussian blue staining method were used to treat the main organs of mice,and the results showed that the multifunctional nanocarrier system owns good safety in mice.Conclusion:Themultifunctional Janus-magneticmesoporoussilica nanocomposites?J-M-MSN/HA-QD?with drug loading,liver cancer targeting and real-time monitoring of drug delivery were successfully prepared,it has been proved that the nanocarrier has good bio-safety in vitro and in vivo and is a kind of nano-drug delivery system with great potential in tumor research.