Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms
PNAS (Proceedings of the National Academy of Sciences)
cell-uptake mechanism, nanoimprint lithography, drug delivery
Biomedical Engineering and Bioengineering | Engineering
Size, surface charge, and material compositions are known to influence cell uptake of nanoparticles. However, the effect of particle geometry, i.e., the interplay between nanoscale shape and size, is less understood. Here we show that when shape is decoupled from volume, charge, and material composition, under typical in vitro conditions, mammalian epithelial and immune cells preferentially internalize disc-shaped, negatively charged hydrophilic nanoparticles of high aspect ratios compared with nanorods and lower aspect-ratio nanodiscs. Endothelial cells also prefer nanodiscs, however those of intermediate aspect ratio. Interestingly, unlike nanospheres, larger-sized hydrogel nanodiscs and nanorods are internalized more efficiently than their smallest counterparts. Kinetics, efficiency, and mechanisms of uptake are all shape-dependent and cell type-specific. Although macropinocytosis is used by both epithelial and endothelial cells, epithelial cells uniquely internalize these nanoparticles using the caveolae-mediated pathway. Human umbilical vein endothelial cells, on the other hand, use clathrin-mediated uptake for all shapes and show significantly higher uptake efficiency compared with epithelial cells. Using results from both upright and inverted cultures, we propose that nanoparticle internalization is a complex manifestation of three shape- and size-dependent parameters: particle surface-to-cell membrane contact area, i.e., particle–cell adhesion, strain energy for membrane deformation, and sedimentation or local particle concentration at the cell membrane. These studies provide a fundamental understanding on how nanoparticle uptake in different mammalian cells is influenced by the nanoscale geometry and is critical for designing improved nanocarriers and predicting nanomaterial toxicity.
Rachit Agarwal, Vikramjit Singh, Patrick Jurney, Li Shi, S. Sreenivasan, and Krishnendu Roy. "Mammalian cells preferentially internalize hydrogel nanodiscs over nanorods and use shape-specific uptake mechanisms" PNAS (Proceedings of the National Academy of Sciences) (2013): 17247-17252. https://doi.org/10.1073/pnas.1305000110
This article originally appeared in PNAS, volume 110, issue 43, 2013, published by the National Academy of Sciences. Authors retain copyright. Non-commercial use only. The article can also be found online at this link. SJSU users: use the following link to login and access the article via SJSU databases.