Contribution of Kupffer cells to liposome accumulation in the liver

Abstract

The liver is a major barrier for site-specific delivery of systemically injected nanoparticles, as up to 90% of the dose is usually captured by this organ. Kupffer cells are thought to be the main cellular component responsible for nanoparticle accumulation in the liver. These resident macrophages form part of the mononuclear phagocyte system, which recognizes and engulfs foreign bodies in the circulatory system. In this study, we have compared two strategies for reducing nanoparticle accumulation in the liver, in order to investigate the specific contribution of Kupffer cells. Specifically, we have performed a comparison of the capability of pegylation and Kupffer cell depletion to reduce liposome accumulation in the liver. Pegylation reduces nanoparticle interactions with all types of cells and can serve as a control for elucidating the role of specific cell populations in liver accumulation. The results indicate that liposome pegylation is a more effective strategy for avoiding liver uptake compared to depletion of Kupffer cells, suggesting that nanoparticle interactions with other cells in the liver may also play a contributing role. This study highlights the need for a more complete understanding of factors that mediate nanoparticle accumulation in the liver and for the exploration of microenvironmental modulation strategies for reducing nanoparticle-cell interactions in this organ.

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

“…In this study, the potential protective effects of BiNPs against apoptotic (ethanol) and oxidative stress‐inducing (hydrogen peroxide) agents were assessed. Macrophages were chosen as an in vitro model of cell stress as the largest portion of intravenously administered nanoparticles (synthetic or biological) are internalized by circulating or resident macrophages 1,41–44. Moreover, macrophages play a major role in tissue regeneration and several studies have demonstrated that the depletion of these cells causes impaired tissue repair 45,46.…”

“…Macrophages were chosen as an in vitro model of cell stress as the largest portion of intravenously administered nanoparticles (synthetic or biological) are internalized by circulating or resident macrophages. [1,[41][42][43][44] Moreover, macrophages play a major role in tissue regeneration and several studies have demonstrated that the depletion of these cells causes impaired tissue repair. [45,46] Cell viability studies demonstrated that both Lipo-NPs and ADSC-EVs protected macrophages from hydrogen peroxide ( Figure 4A) and ethanol-induced stress ( Figure 4B) to a similar extent.…”

The Dual Role of the Liver in Nanomedicine as an Actor in the Elimination of Nanostructures or a Therapeutic Target

“…Kupffer cells (that represent 80-90% of total body macrophages) are responsible for the most part of phagocytic activity in the liver. Kupffer cells, together with blood-circulating monocytes and splenic (red pulp and marginal zone) macrophages, constitute the mononuclear phagocyte system (MPS), which is responsible for the sequestration of more than 95% of NPs which consequently fail to reach their specific target [21,22]. e uptake rate of NPs depends strongly on size, surface charge and ligand chemistry, and shape.…”

Critical considerations for targeting colorectal liver metastases with nanotechnology

“…Moreover, increasing the length of PEG (30 kDa) allowed vectors to evade KC scavenging (Prill et al, ). However, approaches looking into depletion of KCs or impeding receptors mediating uptake, displayed little impact on the cell‐mediated accumulation of NPs (Park et al, ; Samuelsson, Shen, Blanco, Ferrari, & Wolfram, ). Such findings denote that other cells in the hepatic microenvironment may also play a contributing role in liver sequestration of NPs.…”