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Endocytosed nanoparticles hold endosomes and stimulate binucleated cells formation
Lin Xia1, Weihong Gu1, Mingyi Zhang1
1CAS Key Laboratory for Biomedical Effects of Nanomaterial & Nanosafety, Institute of High Energy Physics, Chinese Academy of Science (CAS), Beijing, 100049, China.
Particle and Fibre Toxicology
|December 1, 2016
Summary
Internalized nanoparticles, like 30 nm polystyrene beads, can cause macrophages to form two nuclei without significant cell death. This occurs by disrupting endosomal transport and cytokinesis, impacting cell division.
Area of Science:
- Cell Biology
- Nanomedicine
- Toxicology
Background:
- Nanoparticles are increasingly used in cellular diagnosis and treatment, utilizing the endocytic pathway for cell targeting.
- Macrophages are being explored as drug carriers and therapeutic targets.
- Internalization of nanoparticles can lead to unexpected cellular events, such as binucleated cell formation, even at non-cytotoxic doses.
Purpose of the Study:
- To investigate the mechanism by which internalized nanoparticles induce the formation of binucleated macrophages.
- To explore the impact of nanoparticle internalization on endosomal trafficking and cytokinesis.
- To assess the effect of nanoparticles on other cell lines.
Main Methods:
- Treatment of macrophages with 30 nm polystyrene beads (Ps nanoparticles) and 30 nm gold nanoparticles (Au-NPs).
- Analysis of endosomal structure and trafficking using microscopy and protein expression studies (Early endosome antigen-1, Ras-related protein-11).
- Evaluation of binucleated cell rates in macrophages, A549, HePG-2, and HCT116 cell lines.
Main Results:
- Internalized 30 nm Ps nanoparticles induced the formation of large vesicle-like structures (LVLS) within endosomes at concentrations under 25 μg/ml.
- These LVLS disrupted endosomal transport to lysosomes and altered the distribution of key proteins involved in cytokinesis.
- A significant increase in binucleated cell rates was observed in macrophages, A549, HePG-2, and HCT116 cells treated with nanoparticles.
Conclusions:
- 30 nm Ps nanoparticles induce binucleated macrophages by forming LVLS that block vesicle transport and disrupt cytokinesis-related protein localization.
- Nanoparticle-induced binucleation is not limited to macrophages, as evidenced by increased rates in A549, HePG-2, and HCT116 cell lines.
- The findings suggest that nanoparticle-induced alterations in endosomal trafficking and cell division mechanisms warrant further investigation for nanomedicine applications.
