H2O2自供应纳米粒子用于化学动力学和协同光动力学疗法,以增强cGAS/STING激活
Ai-Hong Zhang1, Wei-Chuang Kong1, Xiao-Lei Zhang1
1College of Laboratory Medicine, Institute of Pathogen Biology and Immunology, Hebei Key Laboratory of Neuropharmacology, Hebei Key Laboratory of Quality & Safety Analysis-Testing for Agro-Products and Food and Zhang Jiakou Key Laboratory of Organic Light Functional Materials, Hebei North University, Zhangjiakou, 075000, Hebei Province, China. liuxuying0045@163.com.
Nanoscale
|March 3, 2025
概括
这项研究开发了一种结合光动力学和化学动力学疗法的纳米粒子,以克服三阴性乳腺癌中免疫抑制性瘤微环境,增强抗瘤活性和免疫治疗潜力.
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:
- 由于转移和预后不佳,三阴性乳腺癌 (TNBC) 存在重大治疗挑战.
- 免疫抑制性瘤微环境 (ITME) 限制了TNBC免疫治疗的疗效.
- 需要新的治疗策略来增强抗瘤活性并克服治疗耐药性.
研究的目的:
- 开发一种新的纳米粒子 (Ce6-CPN@CDC),用于联合光动力学疗法 (PDT) 和化学动力学疗法 (CDT).
- 调查纳米粒子提高ITME和增强TNBC中抗瘤功效的能力.
- 评估这种多模式协同疗法在TNBC治疗中的潜力.
主要方法:
- 铜过氧化物纳米点 (CPN) 和e6 (Ce6) 的封装在一个用肉甲二聚体 (CDC) 功能化的脂质体内.
- 在体外和体内研究评估纳米粒子介导的活性氧物种 (ROS) 生成,DNA损伤和免疫路径激活.
- 对抗瘤活性,瘤抑制和有毒副作用的评估.
主要成果:
- 在酸性瘤环境中,Ce6-CPN@CDC纳米粒子释放H2O2和Cu2+,产生用于CDT的基 (̇OH).
- 对于PDT而言,NIR激光照射Ce6生成的单点氧 (1O2).
- 由ROS诱导的免疫细胞死亡 (ICD) 和DNA损伤激活了cGAS-STING通路,改善了ITME和免疫刺激作用.
- 在体外和体内观察到有效的瘤抑制与最小的毒性.
结论:
- Ce6-CPN@CDC纳米粒子为结合PDT和CDT以激活免疫疗法提供了一个有前途的平台.
- 这种方法提供了一种新的策略,以提高TNBC多式联动疗法的疗效.
- 这项研究表明,对于TNBC等难治性恶性瘤来说,一种新的治疗范式.
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