在活体中毒性和响应pH之间的关系在晶体管类pH敏感纳米洗剂中
Weinan Zhang1,2, Xiaochuan Wang1,3, Jihong Wang1,4
1School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 511442, P. R. China.
Small methods
|December 16, 2024
概括
设计低酸度响应材料 (saRMs) 需要仔细控制pH值. 这项研究表明,具有较低过渡pH值的质子晶体管纳米洗剂 (pTNTs) 可以在健康组织中最大限度地降低毒性.
科学领域:
- 生物材料科学 生物材料科学
- 纳米技术 纳米技术
- 化学生物学 化学生物学
背景情况:
- 针对性疾病成像和治疗中,对子度响应材料 (saRMs) 是至关重要的.
- 设计具有精确pH响应的saRM是具有挑战性的,因为有病和健康组织之间的微妙pH差异.
- 目前针对saRM的pH响应设计的指南不足以最大限度地减少非目标效应.
研究的目的:
- 调查质子晶体管纳米洗剂 (pTNTs) 的响应pH与其体内毒性之间的相关性.
- 建立saRM的设计原则,实现治疗性pH值范围,同时避免正常组织反应.
- 描述pTNTs在pH过渡点范围内的膜解活性和细胞毒性.
主要方法:
- 合成和表征了五种具有明显过渡pH (pHt) 值的pTNT变体 (7.2,7.1,6.9,6.8,6.7).
- 评估了依赖于pH值的从不活跃到活跃状态的过渡,评估了膜解活性和细胞毒性.
- 向小鼠静脉注射pTNT,并监测器官毒性,特别是肝毒性和心脏毒性.
主要成果:
- 在pTNT pHt和体内毒性之间观察到显著的相关性.
- 具有7.2或7.1的pHt的pTNT诱导了显著的肝毒性和心脏毒性.
- 具有6.8-6.7的pHt值的pTNTs没有显著的毒性,表明更安全的治疗窗口.
- 肝毒性与组织微环境中的膜解活性的pH依赖激活有关.
结论:
- 过渡 pH (pHt) 是设计具有最小化 in vivo 毒性的 saRM 的关键参数.
- 具有较低pHt值 (6.8-6.7) 的质子晶体管纳米洗剂 (pTNT) 为响应pH值的应用提供了更安全的配置.
- 这项研究为开发有效和安全的pH响应膜分解材料和saRM提供了必要的指导.
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