工程益生菌的代谢劫持重编程瘤代谢和免疫微环境以进行自我强化的光动力免疫疗法
Shurong Qin1,2, Qi Wang3, Zhuangwei Zhang4
1Department of Gastric and Hernia Surgery, Nanjing Drum Tower Hospital, College of Engineering and Applied Sciences, State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210023, China.
Journal of the American Chemical Society
|October 8, 2025
概括
这项研究引入了一种新型的纳米粒子细菌系统,可以消耗甘氨酸并产生增强光动力免疫疗法 (PDT) 的光敏剂. 这种方法通过重编程瘤代谢和免疫反应来增强抗瘤免疫力和增长抑制.
科学领域:
- 生物医学工程
- 癌症治疗
- 免疫学
背景情况:
- 瘤代谢重编程对于癌症的进展和免疫规避至关重要.
- 目前的光动力免疫疗法 (PDT) 策略缺乏代谢干扰和免疫激活之间的协同协调.
- 开发完善癌症治疗的综合系统是一个重大挑战.
研究的目的:
- 设计用于协同光动力学免疫治疗的混合上转化纳米粒子 (UCNP) - 细菌系统.
- 通过协调代谢干扰和免疫激活来实现自我增强的治疗效果.
- 通过有针对性的代谢重编程和免疫刺激来增强抗瘤功效.
主要方法:
- 工程化大肠杆菌益生菌合成5-氨基氨酸 (PpIX前体) 并使用甘氨酸作为唯一的碳来源.
- 开发了一种UCNP-DNA混合系统,用于针对细菌和miRNA-21反应.
- 通过微流体芯片选,优化细菌功能以检测糖氨酸耗尽和PpIX丰富.
主要成果:
- 这种UCNP-细菌系统有效地消耗了瘤糖氨酸,并产生了原氨酸IX (PpIX).
- 甘氨酸耗尽破坏了瘤氧化还原稳定,增强了光敏剂生成和光动力疗法 (PDT) 的有效性.
- 该系统促进了ROS介导的免疫细胞死亡,树突细胞激活和M1巨细胞分化,导致显著的抗瘤作用和减少转移.
结论:
- 设计的UCNP-细菌混合系统为自我强化的光动力免疫疗法提供了一个新的策略.
- 这种双重代谢方法有效地重新编程瘤微环境,增强免疫细胞死亡,并抑制瘤生长和转移.
- 通过将新陈代谢调节与免疫治疗相结合, 这种综合系统有望促进癌症治疗.
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