Macrophage Scavenger Receptor A Mediates The Uptake of Gold Colloids by Macrophages In Vitro

Abstract

Aims While numerous studies have reported on nanoparticle uptake by phagocytic cells, the mechanisms of this uptake are poorly understood. A metastudy of research focusing on biological particulate matter has postulated that nanoparticles cannot be phagocytosed and therefore must enter cells via pinocytosis. The purpose of this study was to identify the route(s) of uptake of gold nanoparticles in vitro and to determine if these route(s) depend on particle size. Materials & Methods The parent RAW264.7 cell line and its derivatives, transduced with a virus carrying siRNA to macrophage scavenger receptor A, were used as model phagocytes. Citrate-stabilized gold colloids were used as model nanoparticles. We used chemical inhibitors known to interfere with specific routes of particulate uptake. We developed multifocal light microscopy methods including multifocal stack analysis with NIH ImageJ software to analyze cell uptake. Results Irrespective of size, gold nanoparticles are internalized by macrophages via multiple routes, including both phagocytosis and pinocytosis. If either route was blocked, the particles entered cells via the other route. Conclusion Gold nanoparticles with hydrodynamic sizes below 100 nm can be phagocytosed. Phagocytosis of anionic gold colloids by RAW264.7 cells is mediated by macrophage scavenger receptor A.

Microscopic Analysis of the Interaction of Gold Nanoparticles with Cells of the Innate Immune System

“…Although both the in vivo and in vitro testing of AuNPs of different sizes are known to sometimes produce contradictory results 17,18 , we first focused on the 35 nm AuNPs as an example for microscopic detection since this size is easier to examine. Our method was based on correlating the signals of the transmitted high energy electrons and the scattered low energy ones coming mainly from the surface.…”

Exploiting Endocytosis for Nanomedicines

“…For example, phagocytosis has been believed for quite some time to be associated uniquely with the uptake of large particles (.1 mm). However, there are several reports that show the phagocytosis of nanometer-sized particles such as viruses (Clement et al 2006;Ghigo et al 2008), gold (Krpetic et al 2010;Franca et al 2011), silver (Park et al 2011), and polymer nanoparticles (Lunov et al 2011), as well as quantum dots .…”

Endocytosis and exocytosis of nanoparticles in mammalian cells

“…It was reported that gold nanoparticles with sizes below 100 nm were phagocytosed via scavenger receptor-mediated phagocytosis. 30 Tsai et al 31 also demonstrated that gold nanoparticles with a size of 4 nm showed the highest uptake in the macrophages based on the number of nanoparticles taken up per cell, compared with those sized 11, 19, 35, and 45 nm. The 4 nm gold nanoparticles exhibited the highest potency in inhibiting tumor necrosis factor (TNF)-α production related to TNR9-mediated innate immune systems.…”