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In the long-term battle against cancer, scientists have been pursuing an ideal treatment that can precisely destroy tumor cells without damaging healthy tissue. A recent study gives us even more confidence in achieving this goal.
2024年4月11日，华东师范大学生命科学学院叶海峰团队在Cell Reports Medicine杂志上发表了题为"Sonogenetics-controlled synthetic designer cells for cancer therapy in tumor mouse models"的研究论文。 他们提出了一种创新的肿瘤治疗手段——利用超声波控制的细胞“生物炸弹”，对肿瘤发起精准攻击。
With the rapid development of synthetic biology technology, an intelligent live drug delivery system has emerged, bringing new hope for the precision treatment of cancer and other diseases. These smart live drugs act like miniature drug factories that can sense pre-set signal inputs and respond precisely to specific lesions such as inflammation, infection, and tumors in the human body. A new tactic: The sonogenetics team has adopted a strategy of sonogenetics, a technique that uses ultrasound to control cellular behavior. The researchers designed and constructed an ultrasound-regulated gene expression system (SINGER) based on the temperature-sensitive transcriptional repressor TlpA39, which can accurately initiate the efficient expression of specific genes by raising the temperature to 39 degrees Celsius under the stimulation of ultrasound.
Design and Characterization of the CER System (Credit: Cell Reports Medicine) The Power of UltrasoundWhen stimulated by ultrasound, engineered bacteria are activated to release the Azurin protein and the immune checkpoint inhibitor PD-L1 nb capable of inducing apoptosis in tumor cells. This spatiotemporal and temporal controllable regulatory mechanism ensures that the therapeutic effect is directly targeted at the tumor cells, while protecting the surrounding healthy cells from harm to the greatest extent.
Ultrasound-Controlled Development of Customized Engineered Bacteria (Credit: Cell Reports Medicine)Precise attack of engineered bacteria directly to the core of the tumor is delivered to the body by intratumoral injection or intravenous injection, and can selectively colonize and proliferate in areas of tumor hypoxia and necrosis. Under the precise control of ultrasound, these "biobombs" are activated inside the tumor, and their expression in situ releases therapeutic drugs that effectively inhibit the growth of the tumor and can even completely remove the tumor.
Application of Ultrasound-Controlled Customized Engineered Bacteria in Cancer Therapy (Credit: Cell Reports Medicine)
Immune synergy: In a variety of mouse tumor models, this ultrasound-regulated engineered bacterium has shown significant anti-tumor effects. Through intratumoral direct injection or blood delivery, the engineered bacteria can precisely locate the tumor area, and under the induction of ultrasound, release powerful anti-cancer proteins such as Azurin protein, which can induce apoptosis of tumor cells, in the core area of the tumor to directly kill tumor cells. In addition, the researchers also explored a therapeutic strategy using a combination of Azurin and the immune checkpoint inhibitor PD-L1 nb, and found that the strategy not only triggered apoptosis of tumor cells, but also activated the body's immune system, thus achieving a dual anti-cancer effect.
超声调控定制化工程菌用于肿瘤治疗机制示意图（Credit: Cell Reports Medicine）
Preliminary studies of future prospects have shown that this ultrasound-controlled-based customized cell therapy has demonstrated good safety and efficacy in animal models. Although current technologies still face the challenge of more precise delivery to deep or metastatic tumors, with the deepening of research and the improvement of related technologies, ultrasound-controlled engineered bacterial therapies are expected to open up a new world of precision medicine and provide patients with more precise and safer treatment options. In the near future, ultrasound-controlled cell "biobombs" are expected to become a powerful weapon against tumors and bring a new dawn to the majority of cancer patients.
This blueprint depicts the anti-tumor action of ultrasound-stimulated engineering bacteria to locally produce and release therapeutic proteins within tumor tissue (Credit: Cell Reports Medicine)
Original link https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791 (24) 00182-4
Editor-in-charge|Explore Jun
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文章来源|“ iNature"
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