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ACS Nano. 2015 Oct 27;9(10):9986-93. doi: 10.1021/acsnano.5b03521. Epub 2015 Oct 7.

The Interplay of Size and Surface Functionality on the Cellular Uptake of Sub-10 nm Gold Nanoparticles.

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Department of Chemistry, University of Massachusetts Amherst , 710 North Pleasant Street, Amherst, Massachusetts 01003, United States.
Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Chinese Academy of Sciences (CAS) , No.11, First North Road, Zhongguancun, Beijing 100190, China.


Correlation of the surface physicochemical properties of nanoparticles with their interactions with biosystems provides key foundational data for nanomedicine. We report here the systematic synthesis of 2, 4, and 6 nm core gold nanoparticles (AuNP) featuring neutral (zwitterionic), anionic, and cationic headgroups. The cellular internalization of these AuNPs was quantified, providing a parametric evaluation of charge and size effects. Contrasting behavior was observed with these systems: with zwitterionic and anionic particles, uptake decreased with increasing AuNP size, whereas with cationic particles, uptake increased with increasing particle size. Through mechanistic studies of the uptake process, we can attribute these opposing trends to a surface-dictated shift in uptake pathways. Zwitterionic NPs are primarily internalized through passive diffusion, while the internalization of cationic and anionic NPs is dominated by multiple endocytic pathways. Our study demonstrates that size and surface charge interact in an interrelated fashion to modulate nanoparticle uptake into cells, providing an engineering tool for designing nanomaterials for specific biological applications.


endocytosis pathway; passive fusion; size-dependent; sub-10 nm gold nanoparticles; surface charge

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