Synthesis Of Responsive Fluorescent Silica Nanoparticles And Their Controlled Drug Release

In this paper, surface-functionalized porous silica nanospheres as controlled drug-delivery carriers were prepared by microemulsion method. Their controlled release behavior was evaluated using aspirin and aminomethylbenzoic acid as model drug and, pH, glutathione and temperature as the responsive means, respectively. Meanwhile, their release behavior can be monitored by embedding SnO₂ quantum dots, grafting auto-fluorescent compounds, and doping fluorescent dye, respectively. The main research contents and conclusions of this paper are as follows:（1） Fabrication of polyethyleneimine modified dendritic fluorescent silica nanoparticles for pH-responsive aspirin deliveryThe pH-responsive fluorescent porous silica（pSiO₂） nanocarriers were developed by encapsulating SnO₂ nanoparticles and coating polyethyleneimine（PEI） layer. SnO₂/porous silica/PEI（SnO₂/pSiO₂/PEI） nanoparticles have an average diameter of 90 nm and center-radial large pore channels. Aspirin was used as test drug to evaluate the releasing behavior of the SnO₂/pSiO₂/PEI nanoparticles. TEM, FT-IR, BET and FL were used to analysis the structure and prosperities of the SnO₂/pSiO₂/PEI nanoparticles. Results indicated that the SnO₂/pSiO₂/PEI nanoparticles displayed excellent pH-responsive release and presented novel drug-dependent fluorescence, which could be used to trace the drug release.（2） Preparation of copolymer modified dendritic silica nanospheres for pH-controlled styptic releaseDendritic tin oxide/silica（pSiO₂） nanoparticles were prepared by emulsion-condensation route. The pH sensitive copolymer shell（chitosan-poly methyl acrylic acid, CS-PMAA） was modified by in situ polymerization. Their structure and properties were characterized by using TEM, HRTEM, XPS and FL. Styptic was used as test drug to evaluate the releasing behavior of SnO₂/pSiO₂/CS-PMAA nanoparticles, which can achieve high drug loading capacity. Results indicated that the SnO₂/pSiO₂/CS-PMAA nanoparticles have greater loading of drug compared to traditional silica, the SnO₂/pSiO₂/CS-PMAA nanoparticles dispalyed visible pH-controlled release behavior.（3） Fabrication of auto-fluorescent porous silica nanoparticles for Glutathione-triggered controlled releaseThe auto-fluorescent glucose-oxidized glutathione（G-GSSG） compounds was synthesized by a chemical method and was subsequently conjugated on the surface of porous SiO₂ nanoparticles to get pSiO₂-G-GSSG nanoparticles. Their release behavior was evaluated by using aminomethylbenzoic acid（AMA） as a drug model. TEM, BET, XPS and FL were used to characterize the composition, structure and prosperities of the samples. Results showed that G-GSSG compounds were successfully applied as fluorescent sensor for the first time, and the pSiO₂-G-GSSG nanoparticles displayed GSH-responsive release and GSH-dependent fluorescence.（4） Preparation of temperature-responsive fluorescent hollow silica nanoparticles and their controlled release of aminomethylbenzoic acid（AMA）Hollow silica nanoparticles doped with fluorescein isothiocyanate（FITC） were synthesized by one-step method then modified by temperature-sensitive poly（n-isopropyl acrylamide）（PNIPAM） to obtain green fluorescent hollow silica nanoparticles. AMA as a drug model was used to evaluate their drug release behavior under different temperature. Results showed that the hollow nanoparticles have good cell permeability and strong fluorescence properties, which can be used for cell imaging and temperature-responsive release.