Sonocatalysis Regulates Tumor Autophagy for Enhanced Immunotherapy

作者：Yihan Fu, Yuchu He, Xindi Wei, Xuwu Zhang, Wenkang Tu, Weili Xue, Zichuang Xu, Zhuo Li, Xiyun Yan, Kelong Fan, Dawei Gao · 发表于：ACS Nano · 年份：2024 · DOI：10.1021/acsnano.4c08468 · 被引用次数：29 · 研究领域：Nanoplatforms for cancer theranostics、Innovative Microfluidic and Catalytic Techniques Innovation、3D Printing in Biomedical Research

Immunotherapy stands as a groundbreaking strategy for cancer treatment, due to its ability to precisely and safely detect and eradicate tumors. However, the efficacy of immunotherapy is often limited by tumor autophagy, a natural defense mechanism that tumors exploit to resist immune attacks. Herein, we introduce a spatiotemporally controlled method to modulate tumor autophagy via sonocatalysis, aiming to improve immunotherapeutic outcomes. Specifically, we synthesized a tumor-targeting nanocatalyst based on a semiconductor heterojunction composed of Barium Titanate (BTO), Black Phosphorus (BP) integrated with Hyaluronic Acid (HA), referred to as BTO/BP-HA. Compared to traditional catalysts, the heterojunction structure enhances energy band bending and rapid electron–hole separation under ultrasonic stimulation, splitting water to generate H 2 . This promotes tumor cell apoptosis by inhibiting mitochondrial respiration and induces immunogenic cell death, triggering immune responses to eliminate tumor cells. However, the concurrent activation of autophagy mitigates the cytotoxic effectiveness of nanocatalysts. Within the nanocatalyst, BP undergoes lysosomal degradation to generate PO 4 3–, which subsequently interacts with H + to generate a conjugated acidic anion, increasing the lysosomal pH. This research ingeniously combines sonocatalysis with tumor autophagy, disrupting the activity of acidic hydrolases to inhibit autophagy, thereby enhancing the immune response and improv...