Hybrid organosilica nanoagent with Fenton-like reaction activity and glutathione depletion for augmented chemo/chemodynamic therapy

Development of efficient and specialized anti-cancer agent is highly desirable for both basic and clinical research. Herein, a multifunctional organosilica nanoagent (MOCL-DOX) loaded with copper ion, arginine, and doxorubicin was designed and prepared. Copper ion (Cu²⁺) and arginine (LA) were doped into the S-S bond-containing degradable organosilica nanocarrier as functional components. S-S bonds were broken under excessive glutathione (GSH) conditions when the nanoagent reached the tumor sites. Simultaneously Cu²⁺ was released, reduced by GSH to Cu⁺, and Cu⁺ selectively converted hydrogen peroxide (H₂O₂) to hydroxyl radical (•OH) by Fenton-like reaction which caused extensive cellular oxidation and even apoptosis. Tumor cell viability and growth were inhibited to a great extent by the combination of CDT and chemotherapy with minimal normal cells toxicity. Thus, the MOCL-DOX nanoagent demonstrates as a novel paradigm for the fabrication of Fenton's nanoagent for efficient cancer therapy with minimal side effects.