Mn2+/Fe3+/Co2+ and Tetrasulfide Bond Co‐Incorporated Dendritic Mesoporous Organosilica as Multifunctional Nanocarriers: One‐Step Synthesis and Applications for Cancer Therapy

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.