工程菌体纳米载体与生物智能等离子体集成,用于个性化和可调节的酶递送,以增强化学动力学治疗
Xiao-Lin Hou1, Bin Zhang1, Kai Cheng1
1Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|April 6, 2024
概括
工程T4菌体提供乳酸氧化酶 (Lox) 来耗尽瘤的乳酸并产生用于化学动力学治疗 (CDT) 的过氧化. 这种方法增强了氧化杀死,抑制了高达78%的瘤.
科学领域:
- 生物技术是生物技术.
- 纳米医学是一种纳米医学.
- 癌症治疗 癌症治疗
背景情况:
- 瘤微环境 (TME) 改造对于有效的癌症治疗至关重要.
- 乳酸在瘤中的积累改变了新陈代谢,促进了生长.
- 开发向纳米载体用于酶输送是一个关键的挑战.
研究的目的:
- 设计一个T4菌体载体 (T4-Lox-DNA-Fe),用于在瘤治疗中进行可定制的酶输送.
- 通过消耗乳酸和增强氧化应激来调节瘤微环境.
- 研究化学动力学疗法 (CDT) 和基因调控对瘤抑制的协同效应.
主要方法:
- 菌体显示技术被用来设计T4菌体显示乳酸氧化酶 (Lox).
- 德克斯铁 (Fe) 被纳入了基于芬顿反应的CDT.
- 开发了一个低氧激活的等离子体,编码一个EPO增强剂和Keap1.
- 工程菌体载体 (TLDF) 用于在体内治疗瘤.
主要成果:
- 工程化菌体显示了大量的Lox酶 (720个菌体),有效地耗尽了乳酸.
- 洛克斯催化反应产生过氧化,增强CDT的疗效.
- 低氧激活的等离子体表达导致Keap1上调和Nrf2下调.
- 结合CDT和基因调节,导致显著的瘤抑制 (高达78%).
结论:
- T4菌体载体为酶输送和TME重塑提供了一个可定制的平台.
- 洛克斯介导的乳酸消耗,CDT和基因调节的综合方法显示出强大的抗瘤活性.
- 这一策略为先进的瘤治疗提供了一个有希望的新途径.
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