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<p>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 <i>autophagy-related gene 7</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月1日

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  • Yisha Wang,
  • Gan Luo,
  • Haiyang Wang,
  • Yue Zheng,
  • Xiao Xu,
  • Wenbin Zhou,
  • Junrong Lin,
  • Baocheng Chen,
  • Yangfu Guo,
  • Yifeng Jin,
  • Meihua Sui

摘要

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.