Dual gatekeepers-modified dendritic mesoporous silica nanoparticles for controlled drug release

It is urgent to develop functional nanocarriers for targeted drug therapy of cancer. This work developed a smart drug controlled release system based on the dendritic mesoporous silica nanoparticle (DMSN) for dual gatekeepers drug delivery. The DMSN-Cys grafted with disulfide bonds appeared as spheres of uniform size with a porous structure, which enabled a drug loading efficiency of 68.32%. Since the protonated amino groups of chitosan were responsive to pH and the disulfide bonds were sensitive to glutathione, the modified 5-Fu@DMSN-Cys/CS can be used for pH/GSH responsive drug delivery. Release behaviors showed excellent drug controlled release effects. Good biocompatibility and pronounced cytotoxicity of 5-Fu@DMSN-Cys/CS were confirmed by cytotoxicity test. Noted specially, the microcosmic adsorption interaction between drug molecules and DMSN-Cys has been evaluated through molecular dynamic simulation. Electrostatic potential and adsorption simulation confirmed that the driving force of 5-Fu adsorption was originated from electrostatic force and hydrogen bonding interaction between the nanocarriers and 5-Fu molecules. These results indicated that 5-Fu@DMSN-Cys/CS could be potential carriers for anticancer drug delivery. Graphical Abstract