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Cell Size as a Primary Determinant in Targeted Nanoparticle Uptake.

Douglas Howard1, Tyron Turnbull1, David J Paterson2

  • 1Future Industries Institute, University of South Australia, Mawson Lakes, Salisbury, South Australia 5095, Australia.

ACS Applied Bio Materials
|August 26, 2022
PubMed
Summary

Cellular nanoparticle uptake is complex and varies by cell size and receptor expression. Targeted gold nanoparticles showed increased uptake in larger fibroblasts, despite smaller cancer cells having higher receptor density, highlighting cell size as a key factor.

Keywords:
cell sizenanoparticlesreceptor-mediated endocytosissingle-cell analysistransferrin receptor

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Area of Science:

  • Nanomedicine and cellular biology
  • Quantitative single-cell analysis of nanoparticle interactions

Background:

  • Nanoparticle (NP) internalization is critical for nanomedicine applications.
  • Cellular uptake is complex, heterogeneous, and influenced by various factors.

Purpose of the Study:

  • To quantitatively assess nanoparticle uptake in different cell types.
  • To investigate the influence of cell size, receptor expression, and density on NP internalization.
  • To explore the effects of targeted NPs on cell characteristics.

Main Methods:

  • Utilized probabilistic statistics on single-cell data.
  • Studied PEG-coated, transferrin receptor-targeted gold NPs.
  • Analyzed uptake in cancer-derived and fibroblast cells.

Main Results:

  • Smaller cancer cells exhibited higher receptor density and more efficient targeted NP uptake.
  • Larger fibroblasts showed greater overall NP uptake due to size and receptor number.
  • Targeted NP uptake strongly correlated with receptor expression, but not when normalized to cell size.
  • Cell size distribution explained NP uptake distribution.
  • Transferrin receptor-targeted NPs altered fibroblast size and receptor expression.

Conclusions:

  • Cell size is a critical determinant of nanoparticle uptake, independent of receptor density when normalized.
  • Skewed cell size distributions significantly impact observed NP uptake heterogeneity.
  • Targeted NPs may interfere with cellular metabolism and nutrient exchange, altering cell regulation.