Mechanism of hard nanomaterial clearance by the liver

By Kim M. Tsoi, S. Macparland, Xuezhong Ma, V. Spetzler, Juan Echeverri, B. Ouyang, S. Fadel, Edward A. Sykes, N. Goldaracena, J. M. Kaths and 8 more. Nature Materials, 2016

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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.

Subfields: Biomaterials, Biomedical Engineering, Pharmaceutical Science

View Paper: https://www.semanticscholar.org/paper/3a11737dee65c658cbb5bfdb47c79265b8aa16c1

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Citations in the corpus

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The role of lipid components in lipid nanoparticles for vaccines and gene therapy (2022, positive): “[106] exploited the dimensions of the fenestrations in the liver, in an alternate way, to increase LNP accumulation in cells other than the Kupffer cells and LSECs that usually take up a significant portion of nanoparticles administered systemically [107].”
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