Shape-dependent cellular uptake of iron oxide nanorods: mechanisms of endocytosis and implications on cell labeling and cellular delivery.

in Nanoscale by Anbu Mozhi Thamizhchelvan, Hedi Ma, Tianhe Wu, Darlene Nguyen, Jonathan Padelford, Ted J Whitworth, Yuancheng Li, Lily Yang, Hui Mao

TLDR

  • This study investigates how the shape and size of nanoparticles affect how they interact with cells. The researchers found that certain nanoparticles were taken up more efficiently by certain cells and that different cells used different ways to take up the nanoparticles. This information could be useful for developing new medical treatments and imaging techniques.

Abstract

The effects of nanoparticle morphology, especially size and shape, on their interactions with cells are of great interest in understanding the fate of nanoparticles in biological systems and designing them for biomedical applications. While size and shape-dependent cell behavior, endocytosis mechanism, and subcellular distribution of nanoparticles have been investigated extensively with gold and other nanoparticles, studies on iron oxide nanoparticles (IONP), one of the most promising and well-thought-of nanomaterials in biomedical applications, were limited. In this study, we synthesized oligosaccharide-coated water-soluble iron oxide nanorods (IONR) with different core sizes (nm) and different aspect ratios (, length/width), such as IONRat 140/6 nm and IONRat 50/7 nm as well as spherical IONP (20 nm). We investigated how their sizes and shapes affect uptake mechanisms, localization, and cell viability in different cell lines. The results of transmission electron microscopy (TEM) and confocal fluorescence microscopic imaging confirmed the internalization of these nanoparticles in different types of cells and subsequent accumulation in the subcellular compartments, such as the endosomes, and into the cytosol. Specifically, IONRexhibited the highest cellular uptake compared to IONRand spherical IONP, 1.36-fold and 1.17-fold higher than that of spherical IONP in macrophages and pediatric brain tumor medulloblastoma cells, respectively. To examine the cellular uptake mechanisms preferred by the different IONR and IONP, we used different endocytosis inhibitors to block specific cellular internalization pathways when cells were treated with different nanoparticles. The results from these blocking experiments showed that IONRenter macrophages and normal kidney cells through clathrin-mediated, dynamin-dependent, and macropinocytosis/phagocytosis pathways, while they are internalized in cancer cells primarilyclathrin/caveolae-mediated and phagocytosis mechanisms. Overall, our findings provide new insights into further development of magnetic IONR-based imaging probes and drug delivery systems for biomedical applications.

Overview

  • The study investigates the effects of nanoparticle morphology on their interactions with cells, specifically focusing on iron oxide nanoparticles (IONP).
  • The study synthesizes oligosaccharide-coated water-soluble iron oxide nanorods (IONR) with different core sizes and aspect ratios, and investigates their uptake mechanisms, localization, and cell viability in different cell lines.

Comparative Analysis & Findings

  • IONRat 140/6 nm and IONRat 50/7 nm exhibited the highest cellular uptake compared to spherical IONP and IONR in macrophages and pediatric brain tumor medulloblastoma cells, respectively. IONR entered macrophages and normal kidney cells through clathrin-mediated, dynamin-dependent, and macropinocytosis/phagocytosis pathways, while they are internalized in cancer cells primarily through clathrin/caveolae-mediated and phagocytosis mechanisms.

Implications and Future Directions

  • The study provides new insights into the development of magnetic IONR-based imaging probes and drug delivery systems for biomedical applications. Future research should focus on further understanding the cellular uptake mechanisms and subcellular distribution of IONR and IONP in different cell types and biological systems.
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