工程 hemolysin-secreting 细菌使细胞内双酸盐自组装能够增强抗瘤免疫力
Long Wang1, Yuchen Wang1, Ruiqi Lei1
1State Key Laboratory of Pharmaceutical Biotechnology, Medical School, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory for Cardiovascular Information and Health Engineering Medicine, Institute of Clinical Medicine, Nanjing Drum Tower Hospital, Medical School, Nanjing University, Nanjing 210093, China; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing 210023, China; Wuxi Xishan NJU Institute of Applied Biotechnology, Anzhen Street, Xishan District, Wuxi 214101, China; Jiangsu Engineering Center of Biointelligent Materials, Nanjing University, Nanjing 210093, China.
工程细菌诱导瘤细胞内使用来自红细胞的铁的zoledronic酸的自我组装. 这种策略增强了抗瘤免疫反应,并改善了癌症治疗.
科学领域:
- 生物医学工程 生物医学工程
- 癌症治疗 癌症治疗
- 药物输送系统 药物输送系统
背景情况:
- 细胞内自我组装增强了药物输送和治疗疗效.
- 佐乐酸的铁化能力使其适合于自组装系统.
- 诱导瘤部位的自我组装对于有效的癌症治疗具有挑战性.
研究的目的:
- 为了工程细菌的瘤特异性细胞内自组合的zoledronic酸.
- 为了利用细菌瘤殖民和红细胞分解进行药物组装.
- 为了研究细菌介导的细胞内自我组装的抗瘤作用.
主要方法:
- 设计了一种分泌血清素的沙门氏菌Typhimurium菌株用于瘤殖民.
- 在瘤中利用透的红细胞 (RBC) 和巨细胞化.
- 血红素酶-1 (HMOX-1) 介导的血红素降解释放铁离子 (Fe2+).
- 协调Fe2+与佐勒龙酸用于细胞内组合的形成.
主要成果:
- 在瘤巨细胞内,Fe-zoledronic酸组合在细胞内形成.
- 组件产生了活性氧物种 (ROS) 并将巨细胞重新编程为抗瘤表型.
- 观察到增强的免疫反应,有助于抗瘤效应.
结论:
- 细菌介导的细胞内自我组装是癌症治疗的可行策略.
- 利用内源铁离子进行组装扩大了自组装方法.
- 工程细菌提供了新的手段来调节瘤的免疫微环境.
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