免疫性辐射疗法通过核心外纳米敏感剂介导的免疫抑制瘤微环境调制来增强抗瘤免疫力
Naihan Huang1, Xiao-Yan Tang2, Wei Meng1
1Guangdong Provincial Key Laboratory of New Drug Screening, Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
ACS nano
|October 9, 2023
概括
这项研究开发了一种新的纳米敏化剂 (UiO@MnS),以提高辐射治疗 (RT) 的有效性. 它重新编程瘤微环境 (TME),以促进对抗癌症的免疫反应.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 癌症研究 癌症研究
背景情况:
- 放射治疗 (RT) 的有效性受到免疫抑制性瘤微环境 (TME) 和辐射吸收不佳的限制.
- 制定提高RT疗效和刺激抗瘤免疫力的策略至关重要.
研究的目的:
- 构建一个核心外纳米敏化剂,UiO@MnS,用于放大RT疗效和诱导免疫性.
- 研究MnS重编程的TME和基于Hf的UIO敏感的RT的机制.
主要方法:
- UiO@MnS核心外纳米敏化剂的合成.
- 在酸性TME中研究MnS对酸敏感性质,用于H2S生产.
- 评估H2S对瘤氧化,HIF-1α表达和催化酶活性的影响.
- 评估Mn2+介导的芬顿式反应及其对细胞循环停止和放射敏感化的影响.
主要成果:
- 在酸性TME中,UiO@MnS有效地产生H2S,通过抑制线粒体呼吸和减少HIF-1α表达来改善瘤氧化.
- H2S抑制了催化酶,增加了H2O2水平,并增强了G2/M细胞周期停止的芬顿式反应.
- 综合策略显著提高了RT的疗效,并诱导了强烈的抗瘤免疫反应.
结论:
- 开发的UiO@MnS纳米敏化剂有效调节免疫抑制的TME,并增强RT诱导的放射敏化.
- 这种方法对放大免疫性RT结果和改善癌症治疗具有重大前景.
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