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结合化学和机械瘤免疫调节使用化半孔纳米粒子

Taylor R Ausec¹, Lisa L Carr¹, Talaial B Alina¹

¹Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO 80303, United States.

ACS applied nano materials

|October 18, 2024

概括

将工程纳米粒子与聚焦超声波相结合,使瘤相关的巨细胞再极化,增强癌症免疫疗法. 这种方法为免疫学上"冷"的瘤提供了一个有希望的治疗策略.

科学领域:

生物医学工程生物医学工程
癌症免疫学癌症免疫学
纳米技术纳米技术

背景情况:

与瘤相关的巨细胞 (TAMs) 经常表现出一种抗炎性表型,阻碍了抗瘤免疫反应.
将TAM重定向为促炎性表型是癌症免疫治疗中的关键策略.
目前的方法主要集中在生物化学刺激上,限制治疗疗效.

研究的目的:

研究化学和机械刺激的协同效应,以增强免疫调节.
设计能够提供免疫调节剂和产生损伤相关分子模式 (DAMPs) 的纳米粒子.
评估这种综合方法在反极化TAM和促进抗瘤免疫力的有效性.

主要方法:

工程化疏水功能化半孔性纳米颗粒 (F108-hMSNs) 来封装Resiquimod.
利用高强度聚焦超声波 (HIFU) 介导的惯性化来诱导癌细胞死亡和DAMP释放.
同时使用F108-hMSNs和HIFU来刺激TAM并评估表型变化.

主要成果:

与单独使用HIFU相比,与F108-hMSNs结合的HIFU显著增加了癌细胞死亡和DAMP生成.
用F108-hMSNs和HIFU治疗导致TAMs中的炎症标志物 (CD86,MHC II,iNOS) 的上调.
在所有测试条件中,综合方法诱导了TAMs中最显著的炎症表型转变.

结论:

使用工程纳米粒子和HIFU同时进行化学和机械激活是TAM再极化的一个强有力的策略.
这种组合方法显示出在免疫学上"冷"瘤中克服免疫抑制的希望.
进一步开发这种双刺激策略可以促进癌症免疫治疗.

关键词:

癌症纳米技术纳米技术聚焦式超声波的使用免疫疗法免疫疗法半孔性二氧化是一种中孔性二氧化在Resiquimod中使用.

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