| The interaction between nanoparticles and biological systems is closely related to their surface morphology.Rough surfaces can increase the contact of nanoparticles with cell membranes and enhance the internalization of nanoparticles,providing the delivery efficiency of nanocarriers.In addition,gold nanoparticles are the most widely used metal nanoparticles in nanomedicine because of their biocompatibility and unique optical properties.The difference in nanostructures causes changes in the resonance of the gold plasma to result in different absorptions.Gold nanoparticles with absorption in the near-infrared region,such as gold nanorods,gold nanocups and gold shells have been studied,and they all have the ability to photoacoustic imaging(PA)/X-ray tomography(CT)imaging and phototherapy.While heterogeneous tumor tissue can contain subpopulations of cancer cells that are resistant to monotherapy,resulting in the inability to completely eliminate tumors,it is important to design a nano-multimodal combination therapy system.Silica has a controlled morphology and is easy to be functionalized,and 1s often used to load small molecule drugs or therapeutic agents.The unique magnetic properties of Fe304 nanoparticles have great potential in biomedical fields such as therapeutic platforms and magnetic resonance imaging.The multifunctional nano-diagnostic agent can be constructed by designing composite nanoparticles based on gold,silica and iron oxide with rough surfaces and functionalized the cationic gene carrier.The main research work is as follows:1.A porous silica shell with a rough/smooth surface as a nanoreactor,in which gold nanorods are grew in situ to construct a rattle structure nanocapsule,and the cavity is used for sorafenib loading.The polymer gene vector CD-PGEA(ethanolamine functionalized two-armed CD-PGMA)was modified to achieve trimodal combination therapy for cancer.This design combines the advantages of surface roughness,near-infrared response,and drug-controlled release for the treatment of liver cancer.We compared the in vitro gene transfection ability of two kinds of nanocapsules with different surface roughness,and found that the nanocapsules with the rough surface are better than the nanocapsules with the smooth surface.Subsequently,by comparing the uptake of the two nanoparticles by cancer cells,it was confirmed that the rough surface structure promoted the interaction between the nanoparticles and the cells.The gene/chemical/photothermal combination therapy and photoacoustic/CT imaging of liver cancer with different surface morphologies nanocapsules were evaluated in vitro and in vivo,and various synergies between photothermal therapy and gene therapy and chemotherapy were found.2.The hydrophobic iron oxide and water-soluble gold nanocups are used as the units.The iron oxide and silica are spontaneously assembled on the outer side of the gold nanocups by emulsion polymerization of styrene to form raspberry structure nanoparticles.In the emulsion,silane coupling agents in the oil phase droplets with mercapto groups captures the gold nanocups in the aqueous phase,and styrene is subsequently polymerized around it,resulting in tetraethyl silicate and tetraoxide in the oil phase.Iron oxide nanoparticles and PS are phase-separated by reduced compatibility,then TEOS hydrolyzed to form silica protrusion coated with ferroferric oxide.The assembled nanoparticles retain the cap shapes of the gold nanocups and have rough surfaces.In addition,the red shift of spectral characteristic absorption peak can be observed.After the modification of the cationic polymer,the photothermal effect and photothermal cycling performance of the material were verified.Moreover,the material has good gene complexing ability and transfection efficiency,which confirms the potential of the multifunctional carrier for cancer treatment. |
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