State Key Laboratory of Metastable Materials Science and Technology, Nano-Biotechnology Key Lab of Hebei Province, Applying Chemistry Key Lab of Hebei Province, Yanshan University, Qinhuangdao 066004, P. R. China.
Department of Oral and Maxillo-Facial Implantology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology; Shanghai Research Institute of Stomatology, Shanghai 200011, China.
ACS Nano. 2024 Oct 22;18(42):28793-28809. doi: 10.1021/acsnano.4c08468. Epub 2024 Oct 8.
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. 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, 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 improving the effectiveness of immunotherapy.
免疫疗法是一种有前途的癌症治疗策略，因为它能够精确和安全地检测和消除肿瘤。然而，免疫疗法的疗效常常受到肿瘤自噬的限制，肿瘤利用这种自然防御机制来抵抗免疫攻击。在这里，我们介绍了一种通过声催化时空控制肿瘤自噬的方法，旨在改善免疫治疗效果。具体来说，我们合成了一种基于由钛酸钡（BTO）、黑磷（BP）与透明质酸（HA）组成的半导体异质结的肿瘤靶向纳米催化剂，称为 BTO/BP-HA。与传统催化剂相比，异质结结构在超声刺激下增强了能带弯曲和快速电子-空穴分离，将水分解生成 H。这通过抑制线粒体呼吸诱导肿瘤细胞凋亡并诱导免疫原性细胞死亡，引发免疫反应以消除肿瘤细胞。然而，自噬的同时激活减轻了纳米催化剂的细胞毒性作用。在纳米催化剂中，BP 经历溶酶体降解生成 PO，随后与 H 相互作用生成共轭酸性阴离子，增加溶酶体 pH 值。这项研究巧妙地将声催化与肿瘤自噬结合起来，破坏酸性水解酶的活性来抑制自噬，从而增强免疫反应，提高免疫治疗的效果。
