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来自瘤的小细胞外囊泡作为治疗纳米粒子输送的障碍物
Ningqiang Gong1,2, Wenqun Zhong3, Mohamad-Gabriel Alameh4
1Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Nature materials
|September 2, 2024
概括
瘤细胞释放小细胞外囊泡 (sEVs),阻碍纳米粒子药物输送. 用Rab27a敲击抑制sEV可以增强纳米粒子积累和瘤治疗疗效.
科学领域:
- 生物医学工程 生物医学工程
- 纳米技术 纳米技术
- 癌症生物学 癌症生物学
背景情况:
- 纳米粒子在药物输送方面表现有前途,临床应用已经存在.
- 在固体瘤中达到高纳米粒子积累是癌症治疗中的一个重大挑战.
研究的目的:
- 为了研究瘤细胞衍生小细胞外囊泡 (sEVs) 在纳米粒子传递到瘤中的作用.
- 确定sEVs是基于纳米粒子的瘤治疗的障碍,并探索克服它的策略.
主要方法:
- 在瘤微环境中研究了纳米粒子和瘤细胞衍生的sEV之间的相互作用.
- 利用Rab27a的基因淘汰来减少sEV分泌.
- 评估了纳米颗粒在瘤中的积累以及脂质纳米颗粒中共递送的mRNA和siRNA的治疗疗效.
主要成果:
- 来自瘤细胞的sEVs与纳米颗粒结合,并将它们运送到肝脏的Kupffer细胞进行降解,阻断瘤的传递.
- 击败Rab27a显著降低了sEV水平,导致瘤中纳米粒子积累的改善.
- 治疗mRNA与Rab27a小干扰RNA在脂质纳米颗粒中的联合封装增强了治疗疗效.
结论:
- 来自瘤细胞的sEVs作为一种防御机制,阻止纳米粒子向瘤输送.
- 准sEV分泌是一种潜在的策略,可以增强基于纳米粒子的瘤疗法.
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