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In this study, novel hyaluronic acid-pH stimuli-responsive lipid membrane mesoporous silica nanoparticles (HA-PL-MSNs) were designed and assembled, with the chemotherapeutic agent doxorubicin (DOX) as the model drug. HA-PL-MSNs exhibited a well-defined mesostructure covered by lipid bilayer and particle size of ~150 nm. The drug loading capacity was up to ~18.2%. DOX release could be effectively retained by the lipid bilayer in pH 7.4 buffer and exhibited a pH-triggered burst release in the acidic condition. Confocal laser scanning microscopy and fluorescence-activated cell sorting showed that HA-PL-MSNs exhibited higher cellular uptake efficiency via CD44 receptor-mediated endocytosis compared with PL-MSNs in HeLa cells. In vitro cytotoxicity studies demonstrated that HA-PL-MSNs could effectively enhance the targeted delivery of DOX and restrain the growth of HeLa cells. This might provide a promising alternative for the development of a targeted anticancer drug delivery system.

Using hyaluronic acid-functionalized pH stimuli-responsive mesoporous silica nanoparticles for targeted delivery to CD44-overexpressing cancer cells