Calcification of Indocyanine Green Laden Dendritic Mesoporous Manganese‐Silicon Nanocomposite for Multiple Oxygen Compensation Enhanced Phototherapy

Abstract Increasing oxygen (O₂) content and down‐regulating the concentration of glutathione (GSH) in tumor microenvironment (TME) by multiple approaches remain critical factors for the promotion of phototherapeutic effect, especially for photodynamic therapy (PDT). Herein, indocyanine green (ICG) laden dendritic mesoporous manganese‐silicon nanocomposite (NC) is designed and subsequently managed with calcification through in situ growth of calcium phosphate (IDMMS@CaP NC). As specific response behavior of the mildly acidic and GSH overexpressed TME, the IDMMS@CaP NC can rapidly collapse when accumulated at the tumor site, liberate Mn²⁺, Ca²⁺, and ICG, simultaneously reduce the concentration of GSH. Mn²⁺ can catalyze endogenous hydrogen peroxide to produce O₂. Overloaded Ca²⁺ induces mitochondrial injury, and reduces cellular metabolism and O₂ consumption. The photothermal effect from ICG with 808 nm laser irradiation can not only cause tumor cells necrosis but also accelerate blood flow to further improve the O₂ content at the tumor site. Consequently, owing to effective GSH depletion and multiple O₂ compensation, the PDT efficiency of ICG can be significantly increased. As proof of concept, the designed multifunctional nanocomposite will provide a general strategy for enhancing the role of phototherapy in cancer therapeutic area.