Cited by 1,926Nanoparticle-Based Drug DeliveryGold and Silver Nanoparticles Synthesis and ApplicationsDendrimers and Hyperbranched Polymers

Nanoparticle Size and Surface Chemistry Determine Serum Protein Adsorption and Macrophage Uptake

Walkey, Carl D., Olsen, Jonathan B., Guo, Hongbo, Emili, Andrew, Chan, Warren C. W.·2012·Journal of the American Chemical Society

Abstract

Delivery and toxicity are critical issues facing nanomedicine research. Currently, there is limited understanding and connection between the physicochemical properties of a nanomaterial and its interactions with a physiological system. As a result, it remains unclear how to optimally synthesize and chemically modify nanomaterials for in vivo applications. It has been suggested that the physicochemical properties of a nanomaterial after synthesis, known as its "synthetic identity", are not what a cell encounters in vivo. Adsorption of blood components and interactions with phagocytes can modify the size, aggregation state, and interfacial composition of a nanomaterial, giving it a distinct "biological identity". Here, we investigate the role of size and surface chemistry in mediating serum protein adsorption to gold nanoparticles and their subsequent uptake by macrophages. Using label-free liquid chromatography tandem mass spectrometry, we find that over 70 different serum proteins are heterogeneously adsorbed to the surface of gold nanoparticles. The relative density of each of these adsorbed proteins depends on nanoparticle size and poly(ethylene glycol) grafting density. Variations in serum protein adsorption correlate with differences in the mechanism and efficiency of nanoparticle uptake by a macrophage cell line. Macrophages contribute to the poor efficiency of nanomaterial delivery into diseased tissues, redistribution of nanomaterials within the body, and potential toxicity. This study establishes principles for the rational design of clinically useful nanomaterials.

Integrity signals

Registry

Crossref · 10.1021/ja2084338

Cites

68 of 68 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Walkey, C. D., Olsen, J. B., Guo, H., Emili, A., & Chan, W. C. W.
Affiliations
University of Toronto (CA)
Corresponding author
Chan, Warren C. W.
Venue
Journal of the American Chemical Society
Published
2012-01-23
Volume
134
Issue
4
Pages
2139-2147
ISSN
  • 0002-7863 (ISSN-L)
  • 1520-5126
OpenAlex
W1990796256
Cited by
1,926
References
68
Citations by year
2026: 81 · 2025: 111 · 2024: 109 · 2023: 133 · 2022: 158 · 2021: 174 · 2020: 160 · 2019: 156 · 2018: 166 · 2017: 169 · 2016: 135 · 2015: 145 · 2014: 117 · 2013: 75 · 2012: 35
FWCI
29.90
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of the American Chemical Society (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research (MOP93532)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Physical Sciences › Materials Science › Electronic, Optical and Magnetic Materials › Gold and Silver Nanoparticles Synthesis and Applications
  • Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
Keywords
gold nanoparticles, serum protein adsorption, macrophage uptake, nanoparticle size, surface chemistry, nanoparticle delivery, nanoparticle toxicity, nanomaterial design, liquid chromatography-tandem mass spectrometry
MeSH terms
Adsorption, Blood Proteins, Gold, Humans, Macrophages, Particle Size, Polyethylene Glycols, Surface Properties, Tissue Distribution, Metal Nanoparticles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review