纳米粒子特性影响单核细胞的跨内皮迁移,Langmuir

当前位置： X-MOL 学术 › Langmuir › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

纳米粒子特性影响单核细胞的跨内皮迁移
Langmuir ( IF 3.7 ) Pub Date : 2022-04-21 , DOI: 10.1021/acs.langmuir.2c00200
Nahal Habibi ₁ , Tyler D Brown _{2,

3} , Kwasi Adu-Berchie _{2,

3} , Stephanie Christau ₁ , Jeffery E Raymond ₁ , David J Mooney _{2,

3} , Samir Mitragotri _{2,

3} , Joerg Lahann _{1,

4}

Affiliation

由于跨越血脑屏障 (BBB) 的挑战，基于纳米粒子的大脑治疗药物的临床影响有限。某些细胞，如单核细胞，具有跨 BBB 迁移的能力，使其成为基于细胞的大脑传递策略的有吸引力的候选者。在这项工作中，我们探索了影响单核细胞结合和单核细胞介导的 BBB 转运的纳米颗粒设计参数。我们使用电流体动力喷射来制备不同尺寸、成分和弹性的纳米颗粒，以解决它们对 THP-1 单核细胞摄取和穿过 BBB 的渗透的影响。体外_人 BBB 模型是使用人脑微血管内皮细胞 (hCMEC/D3) 开发的，用于评估迁移。我们比较了各种尺寸的聚合物和合成蛋白质纳米粒子 (SPNP) 的单核细胞摄取，以及它们对细胞迁移的影响。SPNPs（人血清白蛋白/HSA 或人转铁蛋白/TF）被证明可以促进单核细胞介导的跨 BBB 的转运超过聚合物纳米颗粒。TF SPNPs (200 nm) 很容易结合，平均每细胞吸收 138 个粒子。纳米颗粒负载显示影响 THP-1 单核细胞的迁移。负载 200 nm TF 和 200 nm HSA SPNPs 的单核细胞的迁移比未处理的对照高 2.3 倍和 2.1 倍。TF SPNP 处理后的 RNA-seq 分析表明，几种迁移基因的上调可能与增加的单核细胞迁移有关（例如整合素亚基 α M 和 α L）。整合素β2链与整合素亚基αM链或整合素亚基αL链结合形成巨噬细胞抗原1和淋巴细胞功能相关抗原1整合素。这两种产品都在跨内皮迁移级联中发挥关键作用。我们的研究结果强调了 SPNPs 作为单核细胞介导的 BBB 转运的药物和/或基因递送平台的潜力，特别是在常规聚合物纳米颗粒无效或不理想的情况下。整合素β2链与整合素亚基αM链或整合素亚基αL链结合形成巨噬细胞抗原1和淋巴细胞功能相关抗原1整合素。这两种产品都在跨内皮迁移级联中发挥关键作用。我们的研究结果强调了 SPNPs 作为单核细胞介导的 BBB 转运的药物和/或基因递送平台的潜力，特别是在常规聚合物纳米颗粒无效或不理想的情况下。整合素β2链与整合素亚基αM链或整合素亚基αL链结合形成巨噬细胞抗原1和淋巴细胞功能相关抗原1整合素。这两种产品都在跨内皮迁移级联中发挥关键作用。我们的研究结果强调了 SPNPs 作为单核细胞介导的 BBB 转运的药物和/或基因递送平台的潜力，特别是在常规聚合物纳米颗粒无效或不理想的情况下。

"点击查看英文标题和摘要"

Nanoparticle Properties Influence Transendothelial Migration of Monocytes

Nanoparticle-based delivery of therapeutics to the brain has had limited clinical impact due to challenges crossing the blood–brain barrier (BBB). Certain cells, such as monocytes, possess the ability to migrate across the BBB, making them attractive candidates for cell-based brain delivery strategies. In this work, we explore nanoparticle design parameters that impact both monocyte association and monocyte-mediated BBB transport. We use electrohydrodynamic jetting to prepare nanoparticles of varying sizes, compositions, and elasticity to address their impact on uptake by THP-1 monocytes and permeation across the BBB. An in vitro human BBB model is developed using human cerebral microvascular endothelial cells (hCMEC/D3) for the assessment of migration. We compare monocyte uptake of both polymeric and synthetic protein nanoparticles (SPNPs) of various sizes, as well as their effect on cell migration. SPNPs (human serum albumin/HSA or human transferrin/TF) are shown to promote increased monocyte-mediated transport across the BBB over polymeric nanoparticles. TF SPNPs (200 nm) associate readily, with an average uptake of 138 particles/cell. Nanoparticle loading is shown to influence the migration of THP-1 monocytes. The migration of monocytes loaded with 200 nm TF and 200 nm HSA SPNPs was 2.3-fold and 2.1-fold higher than that of an untreated control. RNA-seq analysis after TF SPNP treatment suggests that the upregulation of several migration genes may be implicated in increased monocyte migration (ex. integrin subunits α M and α L). Integrin β 2 chain combines with either integrin subunit α M chain or integrin subunit α L chain to form macrophage antigen 1 and lymphocyte function-associated antigen 1 integrins. Both products play a pivotal role in the transendothelial migration cascade. Our findings highlight the potential of SPNPs as drug and/or gene delivery platforms for monocyte-mediated BBB transport, especially where conventional polymer nanoparticles are ineffective or otherwise not desirable.

更新日期：2022-04-21

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南