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通过增加生物活性C6胺水平,用热消耗性聚焦超声波治疗固体瘤

E Andrew Thim¹, Todd Fox², Tye Deering²

¹Department of Biomedical Engineering, University of Virginia, Box 800759, Charlottesville, VA, 22908, USA.

Drug delivery and translational research

|June 19, 2023

概括

稀疏扫描热移除 (TA) 显著提高了C6-胺载荷纳米脂质体 (CNLs) 到瘤的输送. 然而,4T1乳腺瘤对C6的耐药性限制了TA和CNLs的协同治疗效果.

科学领域:

在瘤学瘤学.
纳米医学是一种纳米医学.
生物技术是生物技术.

背景情况:

稀疏扫描带有聚焦超声波 (FUS) 的部分热切除除 (TA) 显示了固体瘤治疗和增强治疗交付的潜力.
载有C6-胺的纳米脂质体 (CNLs) 使用增强透和保留 (EPR) 效应来提供固体瘤,目前正在临床试验中.

研究的目的:

研究CNLs与TA结合用于控制4T1乳腺瘤的协同效应.
评估TA对中枢红细胞输送和瘤内胺积累的影响.

主要方法:

在4T1乳腺瘤模型上使用稀疏扫描TA与FUS.
管理CNL和控制"幽灵"纳米脂质体 (GNL) 来评估治疗效果.
量化内内胺和斯芬戈-1-酸盐 (S1P) 的水平.
进行了体外研究,以评估4T1细胞对C6-胺的耐药性.

主要成果:

单独治疗CNL显示通过EPR内C6积累,但无法控制瘤的生长.
与单独使用EPR相比,TA显著增加了生物活性C6的积累量约12.5倍.
TA + CNL治疗诱导了胺比率的变化 (例如,C16/24,C18/24),但没有改善瘤控制的TA + GNL.
4T1细胞在体外表现出对C6-胺的高耐药性,被确定为缺乏协同作用的可能原因.

结论:

稀疏扫描TA在增强CNL输送和改变瘤中的陶胺配置上是有效的.
瘤细胞对C6-胺的抗性是限制某些固体瘤中TA和CNL之间的治疗协同作用的关键因素.
可能需要进一步的研究来克服C6耐药性以获得有效的组合疗法.

关键词:

陶胺是一种陶胺.聚焦式超声波的使用方法纳米脂质体中的纳米脂质体热性消去是一种热性消去.

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