Mesoporous silica nanoparticles capped with fluorescence-conjugated cyclodextrin for pH-activated controlled drug delivery and imaging

Abstract Herein, we developed a kind of functionalized mesoporous silica nanoparticles with excellent biocompatibility by using fluorescence-conjugated β-cyclodextrin as acid activated gatekeepers to cap the mesopores of mesoporous silica nanoparticles. One hand, 3-carboxy-5-nitrophenylboronic acid, which served as a linker to connect mesoporous silica nanoparticles and fluorescent β-cyclodextrin, was grafted on the surface of the mesoporous silica nanoparticles. Due to the reversible pH-depended phenyboronates formed between 3-carboxy-5-nitrophenylboronic acid and β-cyclodextrin, this functionalized mesoporous silica nanoparticles showed excellent acid-sensitivity. At neutral aqueous, the functionalized mesoporous silica could accommodate the drug molecules because the mesopores were capped by the gatekeepers, while at acid intercellular environment, the gatekeeper would be removed to release the loaded drug due to the hydrolysis of phenyboronates. On the other hand, the fluorescent agents, fluorescein isothiocyanate, could trace the pathway during the therapy process. In vitro drug release behavior further confirmed that the acid-sensitive gatekeeper could control the release of the loaded-drug by the on-off of the pores. Cell experiment analyses against HeLa and HepG2 cells showed clear evidence that DOX-loaded functional mesoporous silica nanoparticles had enhanced tumor inhibition with monitoring the treatment process, indicating a possible therapeutic application for further biomedical use.