一个多重刺激响应的纳米CRISPR克服了瘤氧还原异质性,以增强光动力疗法
Jin Yang1, Liping Bai1, Meiling Shen1
1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
ACS nano
|June 13, 2023
概括
这项研究引入了一种新的纳米CRISPR系统,该系统可使回氧-异质瘤均质化,通过向低氧诱导因子-1α (HIF-1α) 和耗尽谷氨来增强光动力疗法 (PDT) 的疗效.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术纳米技术
- 癌症治疗 癌症治疗
背景情况:
- 瘤氧化还原异质性对传统光动力学疗法 (PDT) 的有效性构成重大挑战.
- 现有的治疗策略难以应对瘤内的多样化的细胞内氧化还原环境.
研究的目的:
- 开发一种新的多重刺激响应纳米CRISPR (Must-nano) 系统,以克服瘤氧化还原异质性.
- 通过基因和表型针对氧化还原失衡来增强瘤特定的可激活PDT.
主要方法:
- 制造Must-nano,包括一个具有CRISPR/Cas9向低氧诱导因子-1α (HIF-1α) 的氧化还原敏感核心和含e6 (Ce6) 的外.
- 利用氨酸酶触发的拆解,电荷逆转和内体体逃生进行细胞内传递.
- 由细胞内氧化还原信号触发的Ce6和CRISPR/Cas9的空间异步释放.
主要成果:
- 纳米必须有效地破坏了HIF-1α和耗尽的谷氨,使 redox-异质瘤细胞均质化.
- 该系统在激光照射下证明了瘤对氧化应激的增强脆弱性和放大氧化损伤.
- 在体外和体内观察到显著的瘤生长抑制和缺氧存活率.
结论:
- 开发的氧化还原同质化策略显著最大限度地提高了PDT对氧化还原异质瘤的疗效.
- 必须纳米提供了一个有希望的策略来克服瘤氧化还原异质性,以改善抗瘤疗法.
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01:59CRISPR
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