Evaluating cell cycle- and autophagy-associated cellular accumulation of lipid-based nanoparticles.

IF 14.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Yisha Wang, Gan Luo, Haiyang Wang, Yue Zheng, Xiao Xu, Wenbin Zhou, Junrong Lin, Baocheng Chen, Yangfu Guo, Yifeng Jin, Meihua Sui
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引用次数: 0

Abstract

Little is known about how cell cycle and autophagy, two fundamental life processes, affect cellular accumulation of nanoparticles. What's even more tough is that several long-lasting methodological barriers have hindered the progress of related research. Here we firstly show the construction of a multi-functional platform for overcoming existing methodological obstacles through integrating multiple technical approaches including autophagy-related gene 7 knockout to specifically block autophagy, PIP-FUCCI transfection and mitotic shake-off to thoroughly separate cell cycle phases, and 3D reconstruction to stereoscopically evaluate cellular accumulation of nanoparticles. Further application of this platform reveals that after a 2-hour incubation of lipid-based nanoparticles, G2-phase and M-phase cells, two populations previously muddled up together as G2/M-phase cells, respectively exhibited the maximum and minimum nanoparticle accumulation. Meanwhile, our data preliminarily suggest enhanced nanoparticle accumulation by autophagy blockade. Besides cell cycle and autophagy, comprehensive statistical analyses reveal a close association between cellular accumulation of nanoparticles and nanoparticle type. This study not only provides a valuable technical strategy, but uncovers important characteristics of cellular accumulation of nanoparticles, offering new insights for optimization and application of nanomedicines.

评估细胞周期和自噬相关的脂基纳米颗粒的细胞积累。
关于细胞周期和自噬这两个基本生命过程如何影响纳米颗粒的细胞积累,人们知之甚少。更棘手的是,几个长期存在的方法障碍阻碍了相关研究的进展。在这里,我们首先展示了构建一个多功能平台,通过整合多种技术方法来克服现有的方法障碍,包括自噬相关基因7敲除以特异性阻断自噬,PIP-FUCCI转染和有丝分裂脱落以彻底分离细胞周期阶段,以及3D重建以立体评估纳米颗粒的细胞积累。进一步应用该平台发现,经过2小时的脂基纳米颗粒,G2期和m期细胞,两个先前混在一起的G2/ m期细胞群体,分别表现出最大和最小的纳米颗粒积累。同时,我们的数据初步表明,自噬阻断可以增强纳米颗粒的积累。除了细胞周期和自噬外,综合统计分析还揭示了纳米颗粒的细胞积累与纳米颗粒类型之间的密切联系。该研究不仅提供了有价值的技术策略,而且揭示了纳米颗粒细胞积累的重要特征,为纳米药物的优化和应用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nature Communications
Nature Communications Biological Science Disciplines-
CiteScore
24.90
自引率
2.40%
发文量
6928
审稿时长
3.7 months
期刊介绍: Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.
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