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A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings.
PLoS One. 2020; 15(7):e0234916.Plos

Abstract

A great deal of attention has been focused on nanoparticles for cancer therapy, with the promise of tumor-selective delivery. However, despite intense work in the field over many years, the biggest obstacle to this vision remains extremely low delivery efficiency of nanoparticles into tumors. Due to the cost, time, and impact on the animals for in vivo studies, the nanoparticle field predominantly uses cellular uptake assays as a proxy to predict in vivo outcomes. Extensive research has focused on decreasing macrophage uptake in vitro as a proxy to delay nanoparticle accumulation in the mononuclear phagocytic system (MPS), mainly the liver and spleen, and thereby increase tumor accumulation. We have recently reported novel synthetic methods employing small molecule crosslinkers for the controlled assembly of small nanoparticles into larger aggregates and found that these nanoaggregates had remarkably high surface coverage and low cell uptake, even in macrophages. We further found that this extremely low cellular uptake could be recapitulated on solid gold nanoparticles by densely coating their surface with small molecules. Here we report our studies on the biodistribution and clearance of these materials in comparison to more conventional PEGylated gold nanoparticles. It was expected that the remarkably low macrophage uptake in vitro would translate to extended blood circulation time in vivo, but instead we found no correlation between either surface coverage or in vitro macrophage cell uptake and in vivo blood circulation. Gold nanoaggregates accumulate more rapidly and to a higher level in the liver compared to control gold nanoparticles. The lack of correlation between in vitro macrophage uptake and in vivo blood circulation suggests that the field must find other in vitro assays to use as a primary proxy for in vivo outcomes or use direct in vivo experimentation as a primary assay.

Authors+Show Affiliations

Department of Molecular Medicine, Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte, California, United States of America.Department of Molecular Medicine, Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte, California, United States of America.Department of Molecular Medicine, Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte, California, United States of America.Department of Molecular Medicine, Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte, California, United States of America.Department of Molecular Medicine, Irell and Manella Graduate School of Biological Sciences, City of Hope National Medical Center, Beckman Research Institute, Duarte, California, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32614882

Citation

Zhang, Yijia, et al. "A Systematic Comparison of in Vitro Cell Uptake and in Vivo Biodistribution for Three Classes of Gold Nanoparticles With Saturated PEG Coatings." PloS One, vol. 15, no. 7, 2020, pp. e0234916.
Zhang Y, Liu AT, Cornejo YR, et al. A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings. PLoS ONE. 2020;15(7):e0234916.
Zhang, Y., Liu, A. T., Cornejo, Y. R., Van Haute, D., & Berlin, J. M. (2020). A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings. PloS One, 15(7), e0234916. https://doi.org/10.1371/journal.pone.0234916
Zhang Y, et al. A Systematic Comparison of in Vitro Cell Uptake and in Vivo Biodistribution for Three Classes of Gold Nanoparticles With Saturated PEG Coatings. PLoS ONE. 2020;15(7):e0234916. PubMed PMID: 32614882.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Systematic comparison of in vitro cell uptake and in vivo biodistribution for three classes of gold nanoparticles with saturated PEG coatings. AU - Zhang,Yijia, AU - Liu,Alice T, AU - Cornejo,Yvonne R, AU - Van Haute,Desiree, AU - Berlin,Jacob M, Y1 - 2020/07/02/ PY - 2019/10/05/received PY - 2020/06/04/accepted PY - 2020/7/3/entrez PY - 2020/7/3/pubmed PY - 2020/7/3/medline SP - e0234916 EP - e0234916 JF - PloS one JO - PLoS ONE VL - 15 IS - 7 N2 - A great deal of attention has been focused on nanoparticles for cancer therapy, with the promise of tumor-selective delivery. However, despite intense work in the field over many years, the biggest obstacle to this vision remains extremely low delivery efficiency of nanoparticles into tumors. Due to the cost, time, and impact on the animals for in vivo studies, the nanoparticle field predominantly uses cellular uptake assays as a proxy to predict in vivo outcomes. Extensive research has focused on decreasing macrophage uptake in vitro as a proxy to delay nanoparticle accumulation in the mononuclear phagocytic system (MPS), mainly the liver and spleen, and thereby increase tumor accumulation. We have recently reported novel synthetic methods employing small molecule crosslinkers for the controlled assembly of small nanoparticles into larger aggregates and found that these nanoaggregates had remarkably high surface coverage and low cell uptake, even in macrophages. We further found that this extremely low cellular uptake could be recapitulated on solid gold nanoparticles by densely coating their surface with small molecules. Here we report our studies on the biodistribution and clearance of these materials in comparison to more conventional PEGylated gold nanoparticles. It was expected that the remarkably low macrophage uptake in vitro would translate to extended blood circulation time in vivo, but instead we found no correlation between either surface coverage or in vitro macrophage cell uptake and in vivo blood circulation. Gold nanoaggregates accumulate more rapidly and to a higher level in the liver compared to control gold nanoparticles. The lack of correlation between in vitro macrophage uptake and in vivo blood circulation suggests that the field must find other in vitro assays to use as a primary proxy for in vivo outcomes or use direct in vivo experimentation as a primary assay. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/32614882/A_Systematic_comparison_of_in_vitro_cell_uptake_and_in_vivo_biodistribution_for_three_classes_of_gold_nanoparticles_with_saturated_PEG_coatings L2 - https://dx.plos.org/10.1371/journal.pone.0234916 DB - PRIME DP - Unbound Medicine ER -
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