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Mechanism of hard-nanomaterial clearance by the liver

Open access
Tsoi, Kim M., MacParland, Sonya A., Ma, Xue-Zhong, Spetzler, Vinzent N., Echeverri, Juan, Ouyang, Ben, Fadel, Saleh M., Sykes, Edward A., Goldaracena, Nicolas, Kaths, Johann M., Conneely, John B., Alman, Benjamin A., Selzner, Markus, Ostrowski, Mario A., Adeyi, Oyedele A., Zilman, Anton, McGilvray, Ian D., Chan, Warren C. W.·2016·Nature Materials

Abstract

The liver and spleen are major biological barriers to translating nanomedicines because they sequester the majority of administered nanomaterials and prevent delivery to diseased tissue. Here we examined the blood clearance mechanism of administered hard nanomaterials in relation to blood flow dynamics, organ microarchitecture, and cellular phenotype. We found that nanomaterial velocity reduces 1000-fold as they enter and traverse the liver, leading to 7.5 times more nanomaterial interaction with hepatic cells relative to peripheral cells. In the liver, Kupffer cells (84.8%±6.4%), hepatic B cells (81.5±9.3%), and liver sinusoidal endothelial cells (64.6±13.7%) interacted with administered PEGylated quantum dots but splenic macrophages took up less (25.4±10.1%) due to differences in phenotype. The uptake patterns were similar for two other nanomaterial types and five different surface chemistries. Potential new strategies to overcome off-target nanomaterial accumulation may involve manipulating intra-organ flow dynamics and modulating cellular phenotype to alter hepatic cell interaction.

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Metadata

Authors
Tsoi, K. M., MacParland, S. A., Ma, X.-Z., Spetzler, V. N., Echeverri, J., Ouyang, B., Fadel, S. M., Sykes, E. A., Goldaracena, N., Kaths, J. M., Conneely, J. B., Alman, B. A., Selzner, M., Ostrowski, M. A., Adeyi, O. A., Zilman, A., McGilvray, I. D., & Chan, W. C. W.
Venue
Nature Materials
Published
2016-08-15
Volume
15
Issue
11
Pages
1212-1221
ISSN
  • 1476-1122 (ISSN-L)
  • 1476-4660
OpenAlex
W2515394036
Cited by
1,010
References
6
FWCI
25.06
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Mechanism of hard-nanomaterial clearance by the liver. https://app.cochat.ai/papers/10.1038/nmat4718
The paper
Tsoi, K. M., MacParland, S. A., Ma, X.-Z., Spetzler, V. N., Echeverri, J., Ouyang, B., Fadel, S. M., Sykes, E. A., Goldaracena, N., Kaths, J. M., Conneely, J. B., Alman, B. A., Selzner, M., Ostrowski, M. A., Adeyi, O. A., Zilman, A., McGilvray, I. D., & Chan, W. C. W. (2016). Mechanism of hard-nanomaterial clearance by the liver. Nature Materials. https://doi.org/10.1038/nmat4718

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.