Near-Infrared Light-Triggered Hydrophobic-to-Hydrophilic Switch Nanovalve for On-Demand Cancer Therapy

An on-demand drug delivery nanoplatform based on mesoporous silica (mSiO₂) coated upconversion nanoparticles (UCNP@mSiO₂) with a novel near-infrared (NIR) light-triggered hydrophobic-to-hydrophilic switch nanovalve was fabricated. The surface of UCNP@mSiO₂ was first immobilized with hydrophobic 2-diazo-1,2-naphthoquinones (DNQ) guest molecules. After doxorubicin hydrochloride (DOX, a universal anticancer drug) was loaded into channels of mSiO₂ shell, β-cyclodextrin (β-CD) host molecules with a hydrophobic cavity were added as gatekeepers to cap DNQ stalk molecules via hydrophobic affinity, which may play a role in the OFF state of the nanovalve to prevent the drug from being released. Upon 980 nm light irradiation, a NIR light-triggered hydrophobic-to-hydrophilic switch, that transformed the hydrophobic guest DNQ into hydrophilic guest 3-indenecarboxylic acid (ICA), took place so that the capped β-CD gatekeepers dissociated due to repulsion between β-CD host (hydrophobic) and ICA guest (hydrophilic), activating the ON state of the nanovalves to release drug. The in vitro studies prove that the nanoplatform enables on-demand drug release to efficiently kill HeLa cell upon NIR light regulation. The in vivo experiment results further confirm that the nanoplatform with such fabricated nanovalves is able to inhibit tumor growth in mice. The designed nanovalves based on the novel NIR light-triggered hydrophobic-to-hydrophilic switch strategy therefore may shed new light on future development of on-demand cancer therapy.