Nanoparticle uptake by circulating leukocytes: A major barrier to tumor delivery

Journal of Controlled Release : Official Journal of the Controlled Release Society
Jamie L BetkerThomas J Anchordoquy

Abstract

Decades of research into improving drug delivery to tumors has documented uptake of particulate delivery systems by resident macrophages in the lung, liver, and spleen, and correlated short circulation times with reduced tumor accumulation. An implicit assumption in these studies is that nanoparticles present in the blood are available for distribution to the tumor. This study documents significant levels of lipoplex uptake by circulating leukocytes, and its effect on distribution to the tumor and other organs. In agreement with previous studies, PEGylation dramatically extends circulation times and enhances tumor delivery. However, our studies suggest that this relationship is not straightforward, and that particle sequestration by leukocytes can significantly alter biodistribution, especially with non-PEGylated nanoparticle formulations. We conclude that leukocyte uptake should be considered in biodistribution studies, and that delivery to these circulating cells may present opportunities for treating viral infections and leukemia.

Citations

Feb 1, 2020·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Luca DigiacomoGiulio Caracciolo
Aug 17, 2019·Nature Communications·Francesca GiulimondiGiulio Caracciolo
Dec 21, 2019·Biochimica Et Biophysica Acta. Biomembranes·Sara PalchettiGiulio Caracciolo
Feb 13, 2021·Biomedical Materials·Themis R KyriakidesWendy C Sheu
Jul 6, 2021·Advanced Drug Delivery Reviews·Danielle E LargeDebra T Auguste
Aug 8, 2021·Acta Biomaterialia·Natalia OnishchenkoElena Vodovozova
Aug 10, 2021·Advanced Drug Delivery Reviews·Melgious Jin Yan AngXiaogang Liu
Oct 31, 2018·Molecular Pharmaceutics·Alexandros Marios SofiasSjoerd Hak
Oct 3, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Andreas Zumbuehl

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