Abstract

Enriching the application of multifunctional dendritic mesoporous organosilica (DMOS) is still challenging in anti-cancer research. Herein, manganese ions, iron ions, or cobalt ions and tetrasulfide bonds are co-incorporated into the framework of DMOS to yield multifunctional nanoparticles denoted as Mn-DMOS, Fe-DMOS, or Co-DMOS by directly doping metal ions during the synthetic process. Due to co-incorporation of metal ions and tetrasulfide bonds, these designed nanocarriers have more functions rather than only for cargo delivery. As proof of concept, the nanocomposite is established based on Mn-DMOS as an efficient nanocarrier for indocyanine green (ICG) delivery and modification with polyethylene glycol. In the tumor microenvironment, the generated hydrogen sulfide (H 2 S) arising from the reaction between tetrasulfide bond and over-expressed glutathione (GSH) causes mitochondrial injury to reduce cellular respiration. The released Mn 2+ from the rapidly decomposed nanocomposite catalyzes the endogenous hydrogen peroxide to produce oxygen (O 2 ). The photothermal effect from the released ICG initiated by the near-infrared light induces cancer cells apoptosis and simultaneously enhances the content of blood O 2 at tumor sites. Therefore, due to the GSH depletion and trimodal O 2 compensation, the photodynamic therapy efficiency of ICG has significantly improved. In brief, these designed nanocarriers will play advanced roles in cancer therapy.