"All-in-one" nano-system for smart delivery and imaging-guided combination therapy of triple-negative breast cancer

Triple-negative breast cancer (TNBC) with highly malignant and aggressive, still faces challenges in treatment due to the single treatment and side effects. It is urgent to develop an advanced theranostic platform against TNBC. Herein, an "all-in-one" nano-system Au/Cu nanodots/doxorubicin@nanospheres (Au/CuNDs/DOX@NS) with dual-responsive properties was designed for dual-mode imaging-guided combination treatment of TNBC. The nano-system was composed of glutathione (GSH)/temperature dual-responsive nanospheres, further loaded with DOX and Au/CuNDs. During in vivo circulation, the nano-system remained in a "dormant" state. Once accumulated at the tumor site by passive targeting, the nano-system was "awakened" by GSH and heating to release DOX and Au/CuNDs. Au/CuNDs, as photothermal agent and nanozyme, could achieve effective photothermal therapy (PTT) and photothermal-enhanced chemodynamic therapy (CDT), which worked together with chemotherapy for cancer treatment. More importantly, Au/CuNDs/DOX@NS-mediated photothermal-enhanced CDT promoted reactive oxygen species (ROS) production, enhanced oxidative stress to promote macrophage polarization, reversed the immunosuppressive microenvironment, and promoted anti-tumor immune responses. Moreover, the nano-system exhibited near-infrared fluorescence imaging and computed tomography imaging, which has potential applications in detection and image-guided precision therapy of TNBC. Therefore, the designed "all-in-one" nano-system integrates intelligent responsiveness, targeted delivery, dual-modal imaging and chemotherapy/PTT/CDT combination treatment into a single system, providing a promising strategy for tumor diagnosis and treatment.