Study Of Spherical/layered Assembly Based On Inorganic Nanomaterial: Preparation And Application In Drug Delivery

The assembly of inorganic nanomaterial is a kind of hybrid material that combines the advantages of different materials and is widely used in many fields such as electronic communication,energy supply,food safety and so on.However,the biomedical application of assemblies based on inorganic nanomaterial is still in its infancy.Therefore,the preparation and biomedical application of novel assembly of inorganic nanomaterial have both theoretical value and practical application prospects.In particular,spherical and layered assemblies of inorganic nanomaterial are favored duo to their large surface area and high loading efficiency.Therefore,in this thesis,three novel assemblies of inorganic nanomaterial have been designed and constructed based on spherical/layered inorganic nanomaterials for controlled release and targeted delivery of anticancer drugs as well as synergistic cancer therapy.The main works are listed as follows:1.Construction of a mesoporous silica nanoparticle and cerium oxide nanoparticle assembly for controlled drug release?stimuli-responsive drug delivery system?A triple-triggered?pH,glutathione and light irradiation?stimuli-responsive nanosystem based on mesoporous silica nanoparticle and cerium oxide nanoparticle assembly has been designed and prepared.In this nanosystem,mesoporous silica nanoparticle was prepared as a vector for doxorubicin and hematoporphyrin,and cerium oxide nanoparticle was adopted as a gatekeeper as well as a quencher for fluorescence of doxorubicin.The drug loading efficiency of doxorubicin was about 21.8?g/mg.Benefiting from the combination of the degradation of cerium oxide nanoparticle via reduced glutathione and low pH as well as the conformal change of hematoporphyrin under light irradation,the more precise release of pre-loaded doxorubicin could be realized.The release efficiency of doxorubicin was about70%.Moreover,under the so-called triple-control,the side effects on normal cells could be avoided to some extent.2.Construction of a folic acid-modified mesoporous silica nanoparticle and layered double hydroxide assembly for targeted chemo/PDT/PTT combinatorial therapy?targeted stimuli-responsive drug delivery system?A folic acid modified targeted nanosystem based on tellurium nanopaticle-in situ formed mesoporous silica nanoparticle and paclitaxel-loaded MgAl layered double hydroxide assembly has been successfully synthesized.The obtained nanosystem MT@L-PTX@FA showed pH-responsive drug release and the release efficiency of paclitaxel was approximately 70%.Moreover,benefiting from the advantages of tellurium nanoparticle,the nanosystem exhibited an efficient in vitro photodynamic therapy?PDT?and photothermal therapy?PTT?activity.Under irradiation?2 W/cm²?,MT@L-PTX@FA?2mg/mL?could generate a certain amount of reactive oxygen species and meanwhile make temperature rise about 50°C.In addition,MT@L-PTX@FA could target cancer cells due to the function of folic acid.In particular,cytotoxicity tests indicated that under near-infrared irradiation,more efficient therapeutic effect could be achieved using MT@L-PTX@FA,benefiting from therapeutic synergy based on chemo/PDT/PTT combinatorial therapy.3.Construction of a layered double hydroxide and MnO₂ nanosheet assembly for optional combination cancer therapy?versatile biodegradable targeted drug delivery system?A facile strategy to design a biodegradable versatile drug delivery nanocarrier?FA-CM?has been developed based on layered double hydroxide and MnO₂ nanosheet assembly.The results of transmission electron microscope and inductively coupled plasma mass spectrometry showed that,FA-CM could be effectively degraded into easily metabolized harmless metal ions to overcome long-term toxic side effects.FA-CM could be used to load positive/negative-charged or hydrophilic/hydrophobic drugs with different loading ratios.Hydrophilic drug doxorubicin and hydrophobic drug paclitaxel were chosen as models to be co-loaded on FA-CM and the optimal loading ratio of them was determined to be 1:1.In vitro and in vivo assays showed that doxorubicin and paclitaxel co-loaded FA-CM exhibited synergistic enhanced therapeutic effect compared with either free drug alone or the corresponding cocktail solutions.Moreover,owing to the function of folic acid,FA-CM could reduce the side effects on normal cells/tissues to some extent.In summary,the above-mentioned three assemblies of inorganic nanomaterial,based on inorganic nanomaterials including mesoporous silica,manganese dioxide and layered double hydroxides,have been designed and used for controlled drug release,targeted delivery and synergistic therapy,separately.Hopefully,these researches can provide new ideas for excavating assemblies of inorganic nanomaterial-based biomedical applications.