Tumor microenvironment responsive theranostic agent for enhanced chemo/chemodynamic/photothermal therapy

The specific characteristics of the tumor microenvironment (TME) and monotherapy always lead to poor therapy effects for tumors. Hereby, we have developed a smart multifunctional theranostic agent-SSMID (Se@SiO₂@MnO₂-ICG/DOX) nanocomposites (NCs) that could intelligently respond to the TME for enhanced chemotherapy/photothermal/chemodynamic therapy guided by magnetic resonance imaging (MRI). The SSMID NCs were composed of indocyanine green (ICG) and doxorubicin hydrochloride (DOX) co-loaded porous Se@SiO₂ @MnO₂. Under the specific conditions of the TME (slightly acidic, H₂O₂ and GSH overexpression), the MnO₂ NPs were specifically decomposed and then SSMID released Mn²⁺, DOX and Se, which played roles in chemodynamic therapy (CDT), chemotherapy, protecting normal tissues and inhibiting tumor cells by modulating reactive oxygen species (ROS), respectively. MnO₂ reacted with glutathione (GSH) and H₂O₂ to generate O₂ and Mn²⁺, which alleviated tumor hypoxia to improve chemotherapy and depleted GSH to enhance oxidative stress for chemodynamic therapy. More importantly, SSMID NCs could simultaneously exert the photothermal therapy (PTT) effect with near-infrared laser irradiation and promote the release of Mn²⁺ and DOX to achieve enhanced chemotherapy/chemodynamic therapy. In addition, the released Mn²⁺ could be used as a T1-weighted MRI contrast agent to monitor tumor location. The SSMID NCs exhibited a pronounced tumor growth inhibitory effect and promising biological safety, which develop a new method to rationally design nano-theranostic agents with enhanced performance for anti-tumor.