可转换的瘤微环境-响应氧气空缺-富含MnO2@Hydroxyapatite纳米球用于高效的癌症声动力免疫疗法
Minxing Li1, Qiyu Liu2, Songzuo Xie1
1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Collaborative Innovation Center for Cancer Medicine, Department of Biotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|February 17, 2025
概括
新的纳米球作为智能声敏化剂,在瘤微环境中释放活性二氧化,以促进癌症免疫治疗. 这种方法有效地打击瘤并增强免疫反应,而不会损害健康组织.
科学领域:
- 生物医学工程 生物医学工程
- 材料科学 材料科学 材料科学
- 纳米技术 纳米技术
背景情况:
- 声动力疗法 (SDT) 显示出免疫治疗的前景,但受到免疫抑制性瘤微环境 (TMEs) 的阻碍.
- 目前的声敏化剂缺乏对TME条件的选择性和响应性,这限制了它们的抗癌疗效.
研究的目的:
- 开发一种先进的,对TME有反应的声敏化剂,用于增强声动力免疫治疗.
- 为了创建富含氧气空缺的MnO2@hydroxyapatite核心外纳米球 (O_v-MO@CPO),可以选择性地准并响应TME.
主要方法:
- 合成的O_v-MO@CPO纳米球,具有pH敏感的酸外和富含氧气空隙的MnO2核心.
- 研究了MnO2核心的TME响应释放及其用于减轻缺氧的催化酶类活性.
- 评估了超声波启动的活性氧物种 (ROS) 生产及其对4T1瘤携带小鼠瘤生长和转移的影响.
- 评估了O_v-MO@CPO介导的SDT与免疫检查点抑制剂的协同效应.
主要成果:
- O_v-MO@CPO纳米球在酸性TME中选择性地释放了活性MnO2核心,减轻了缺氧并增加了H2O2消耗.
- 在MnO2中优化氧气空缺,通过促进电子孔对分离,促进了超声波启动的ROS生产.
- 在小鼠中观察到有效抑制瘤生长和转移,在正常组织中没有显著的毒性.
- 与免疫检查点抑制剂的联合治疗进一步改善了治疗结果.
结论:
- O_v-MO@CPO作为一个有效的TME-依赖的sonosensitizer用于声动力免疫疗法.
- 这种方法显示出克服TME诱导的免疫抑制和增强抗癌疗效的巨大潜力.
- 开发的纳米平台为下一代声动力免疫疗法提供了一个有前途的战略.
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