Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Monash Suzhou Research Institute, Monash University, Suzhou, 215000, China.
Adv Mater. 2024 Aug;36(33):e2401974. doi: 10.1002/adma.202401974. Epub 2024 Jun 26.
Currently, sonodynamic therapy (SDT) has limited therapeutic outcomes and immune responses, highlighting the urgent need for enhanced strategies that can stimulate robust and long-lasting antitumor effects. Microcystis, a notorious microalga, reveals the possibility of mediating SDT owing to the presence of gas vesicles (GVs) and phycocyanin (PC). Herein, a nontoxic strain of Microcystis elabens (labeled Me) is developed as a novel agent for SDT because it generates O under red light (RL) illumination, while GVs and PC act as cavitation nuclei and sonosensitizers, respectively. Moreover, algal debris is released after ultrasound (US) irradiation, which primes the Toll-like receptor pathway to initiate a cascade of immune responses. This sono-immune strategy inhibits CT26 colon tumor growth largely by promoting dendritic cell (DC) maturation and cytotoxic T-cell activation. After combination with the immune checkpoint blockade (ICB), the therapeutic outcome is further amplified, accompanied by satisfactory abscopal and immune memory effects; the similar potency is proven in the "cold" 4T1 triple-negative breast tumor. In addition, Me exhibits good biosafety without significant acute or chronic toxicity. Briefly, this study turns waste into wealth by introducing sono-immunotherapy based on Microcystis that achieved encouraging therapeutic effects on cancer, which is expected to be translated into the clinic.
目前，声动力学疗法（SDT）的治疗效果和免疫反应有限，这凸显了迫切需要增强策略以刺激强大而持久的抗肿瘤作用。微囊藻是一种臭名昭著的微藻，由于存在气室（GVs）和藻蓝蛋白（PC），它有可能介导 SDT。在此，将无毒的微囊藻属（命名为 Me）菌株开发为 SDT 的新型制剂，因为它在红光（RL）照射下产生 O，而 GVs 和 PC 分别作为空化核和声敏剂。此外，超声（US）照射后会释放藻类碎片，从而启动 Toll 样受体途径引发一连串的免疫反应。这种声免疫策略主要通过促进树突状细胞（DC）成熟和细胞毒性 T 细胞激活来抑制 CT26 结肠肿瘤生长。与免疫检查点阻断（ICB）联合使用后，治疗效果进一步放大，同时伴有令人满意的远隔和免疫记忆效应；在“冷”的 4T1 三阴性乳腺癌中也证明了类似的功效。此外，Me 表现出良好的生物安全性，没有明显的急性或慢性毒性。简而言之，本研究通过引入基于微囊藻的声免疫疗法，将废物转化为财富，实现了对癌症的令人鼓舞的治疗效果，有望转化为临床应用。
