Ultrasound-Responsive Nanobubbles for Breast Cancer: Synergistic Sonodynamic, Chemotherapy, and Immune Activation through the cGAS-STING Pathway

作者：Huan Pu, Jia Huang, Bin Gui, Yueying Chen, Yuxin Guo, Yingtao Lian, Juhong Pan, Yugang Hu, Nan Jiang, Qing Deng, Qing Zhou · 发表于：ACS Applied Materials & Interfaces · 年份：2025 · DOI：10.1021/acsami.4c21493 · 被引用次数：19 · 研究领域：Nanoplatforms for cancer theranostics、Cancer Research and Treatments、Amoebic Infections and Treatments

Breast cancer remains the leading cause of cancer-related deaths among women worldwide, necessitating more effective treatment strategies. Chemotherapy combined with immunotherapy is the first-line treatment for breast cancer, but it still suffers from limited therapeutic efficiency and serious side effects, which are usually due to the poor delivery efficiency, drug resistance of tumor cells, and immunosuppressive tumor microenvironment. This study explores the development of ultrasound-responsive nanobubbles (Ce6/PTX Nbs) for targeted imaging and sonoimmunotherapy in breast cancer treatment. By integrating sonodynamic therapy (SDT), chemotherapy, and immunotherapy, the nanobubbles aim to address challenges such as poor drug delivery, systemic toxicity, and immune suppression in conventional therapies. The nanobubbles, composed of sonosensitizer chlorin e6 (Ce6)-modified phospholipid and loaded with the chemotherapeutic agent paclitaxel (PTX) enhancing drug-loading capacity, are designed to precisely target tumor sites via cyclic-RGD peptides. Upon ultrasound activation, Ce6 induces reactive oxygen species (ROS), promoting immunogenic cell death (ICD), while PTX disrupts tumor cell mitosis, enhancing the immune response. The nanobubbles' ultrasound responsiveness facilitates real-time imaging and controlled drug release, maximizing therapeutic efficacy while minimizing side effects. Key findings demonstrate that Ce6/PTX Nbs significantly reduced tumor growth in a 4T1 breast ...