The multi-stimuli responsive drug delivery system has recently attracted attention in
cancer treatments, since it can reduce several side effects and enhance
cancer therapeutic efficacy. Herein, we present the intracellular
antioxidant (
glutathione, GSH),
enzyme (
hyaluronidase, HAase), and
hydrogen peroxide (H2O2) triggered mesoporous organo-
silica (MOS) nanocomposites for multi-modal treatments via chemo-, photothermal, and photodynamic
cancer therapies. A MOS nanoparticle was synthesized by two-types of precursors,
tetraethyl orthosilicate (TEOS) and bis[3-(triethoxysilyl)propyl] tetrasulfide (BTES), providing large-sized mesopores and
disulfide bonds cleavable by GSH. Additionally, we introduced a new β-
cyclodextrin-
hyaluronic acid (CDHA) gatekeeper system, enabling nanocomposites to form the specific interaction with the
ferrocene (Fc) molecule, control the drug release by the HAase and H2O2 environment, as well as provide the targeting ability against the CD44-overexpressing
melanoma (B16F10) cells.
Indocyanine green (ICG) and
doxorubicin (Dox) were loaded in the MOS-Fc-CDHA (ID@MOS-Fc-CDHA) nanocomposites, allowing for
hyperthermia and cytotoxic
reactive oxygen species (ROS) under an 808 nm NIR
laser irradiation. Therefore, we demonstrated that the ID@MOS-Fc-CDHA nanocomposites were internalized to the B16F10 cells via the CD44 receptor-mediated endocytosis, showing the controlled drug release by GSH, HAase, and H2O2 to enhance the
cancer therapeutic efficacy via the synergistic chemo-, photothermal, and
photodynamic therapy effect.