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性纳米酶对巨细胞的依赖性重编程
Yu Zhang1,2, Tingting Cui1,2, Jie Yang1,2
1Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, P. R. China.
Angewandte Chemie (International ed. in English)
|June 13, 2023
概括
状纳米酶利用状特异性相互作用产生细胞外活性氧物种 (ROS),有效地重聚瘤相关巨细胞 (TAMs) 以增强癌症免疫疗法.
科学领域:
- 纳米技术纳米技术
- 免疫治疗是一种免疫疗法.
- 材料科学 材料科学 材料科学
背景情况:
- 细胞外活性氧物种 (ROS) 对于调节抑制瘤 (M1) 巨细胞极化至关重要.
- 目前的纳米平台往往无法在巨细胞附近积累,主要产生细胞内ROS,限制治疗效果.
- 瘤相关巨细胞 (TAMs) 有助于瘤免疫抑制,需要用于其再极化策略.
研究的目的:
- 设计和合成用于调节TAM偏振的合性二硫化物/二硫化物 (MoS2/CoS2) 纳米酶.
- 研究性在纳米酶药理动力学,瘤积累和与巨细胞相互作用中的作用.
- 开发一种用于细胞外ROS生成的新策略,通过M1 TAM再极化逆转瘤免疫抑制.
主要方法:
- 合成具有类似过氧化酶 (POD) 和类似催化酶 (CAT) 活动的性MoS2/CoS2纳米酶.
- 对d-chiral,l-chiral和dl-racemate纳米粒子 (NP) 的药理动力学,瘤积累和细胞吸收的评估.
- 在瘤微环境 (TME) 中评估TAM再极化和治疗效应.
主要成果:
- 与l-NPs和dl-NPs相比,d-chiral MoS2/CoS2 NPs (d-NPs) 显示出增强的药理动力学,更长的半衰期和更高的瘤积累.
- d-NPs有效地产生了细胞外基 (⋅OH) 和氧 (O2),将TAM重新极化为M1表型.
- l-NPs显示出高细胞吸收由于性驱动的粘附,导致有限的M1极化.
结论:
- 基质MoS2/CoS2纳米酶可以被设计为细胞外ROS生成器,用于向癌症免疫疗法.
- 性在纳米酶-生物相互作用中发挥着关键作用,影响生物分布和治疗结果.
- 这项研究提出了一种新的方法,使用奇拉纳米酶来重编程TAM并克服瘤免疫抑制.
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