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

Yisha Wang, Gan Luo, Haiyang Wang, Yue Zheng, Xiao Xu, Wenbin Zhou, Junrong Lin, Baocheng Chen, Yangfu Guo, Yifeng Jin and Meihua Sui ()
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Yisha Wang: Zhejiang University School of Medicine
Gan Luo: Zhejiang University School of Medicine
Haiyang Wang: Zhejiang University School of Medicine
Yue Zheng: Zhejiang University School of Medicine
Xiao Xu: Hangzhou Medical College
Wenbin Zhou: Zhejiang University School of Medicine
Junrong Lin: Zhejiang University School of Medicine
Baocheng Chen: Zhejiang University School of Medicine
Yangfu Guo: Zhejiang University School of Medicine
Yifeng Jin: Zhejiang University School of Medicine
Meihua Sui: Zhejiang University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60962-4

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