Light-Responsive, Singlet-Oxygen-Triggered On-Demand Drug Release from Photosensitizer-Doped Mesoporous Silica Nanorods for Cancer Combination Therapy

Smart drug delivery systems with on-demand drug release capability are rather attractive to realize highly specific cancer treatment. Herein, a novel light-responsive drug delivery platform based on photosensitizer chlorin e6 (Ce6) doped mesoporous silica nanorods (CMSNRs) is developed for on-demand light-triggered drug release. In this design, CMSNRs are coated with bovine serum albumin (BSA) via a singlet oxygen (SO)-sensitive bis-(alkylthio) alkene (BATA) linker, and then modified with polyethylene glycol (PEG). The obtained CMSNR-BATA-BSA-PEG, namely CMSNR-B-PEG, could act as a drug delivery carrier to load with either small drug molecules such as doxorubicin (DOX), or larger macromolecules such as cis-Pt (IV) pre-drug conjugated third generation dendrimer (G3-Pt), both of which are sealed inside the mesoporous structure of nanorods by BSA coating. Upon 660 nm light irradiation with a rather low power density, CMSNRs with intrinsic Ce6 doping would generate SO to cleave BATA linker, inducing detachment of BSA-PEG from the nanorod surface and thus triggering release of loaded DOX or G3-Pt. As evidenced by both in vitro and in vivo experiments, such CMSNR-B-PEG with either DOX or G3-Pt loading offers remarkable synergistic therapeutic effects in cancer treatment, owing to the on-demand release of therapeutics specifically in the tumor under light irradiation.