Rapid Uptake of Gold Nanorods by Primary Human Blood Phagocytes and Immunomodulatory Effects of Surface Chemistry

Abstract

Nanoparticle-based in vivo applications should consider the omnipresence of the phagocytes in the bloodstream and tissue. We have studied the nanoparticle uptake capacities of the most important human primary leukocyte populations using a nanoparticle library encompassing both rod-shaped and spherical gold nanoparticles with diameters between 15 and 50 nm and a variety of surface chemistries. Cetyltrimethylammoniumbromide (CTAB)-stabilized nanoparticles were internalized rapidly within 15 min and in large amounts by macrophages and to a lower extent also by monocytes. Interestingly, we found that the uptake of nanorods by macrophages was more efficient than that of nanospheres. Blocking experiments and electron microscopic studies revealed macropinocytosis as the major uptake mechanism. Grafting of poly(ethylene oxide) (PEO) onto the nanorods was found to significantly delay their internalization for several hours. The long-term uptake of PEO-coated nanoparticles with positively or negatively charged end groups was almost identical. Particle surface chemistry strongly influenced the expression of inflammation-related genes within 1 day. Furthermore, the macrophage phenotype was significantly affected after 7 days of culture with nanorods depending on the surface chemistry. Thus, in vivo application of nanoparticles with certain surface functionalities may lead to inflammation upon particle accumulation. However, our data also suggest that chemical modifications of nanoparticles may be useful for immunomodulation.

Size-Dependent Attenuation of TLR9 Signaling by Gold Nanoparticles in Macrophages

“…Many nanomaterials have been reported to induce inflammatory responses, such as silica nanoparticles, cetyltrimethylammonium bromide-coated gold nanorod, and titanium dioxide nanoparticles (43)(44)(45). However, few studies have focused on the effect of nanoparticles on TLR stimulation.…”

Intracellular disposition of chitosan nanoparticles in macrophages: intracellular uptake, exocytosis, and intercellular transport

“…The endocytosis of NMs by macrophages has been well documented in the literature, [5][6][7][8][9] and it has been reported that NMs with high surface charge and large particle size are phagocytized more efficiently by macrophages. 6,7 The shape of NMs has a profound impact on their endocytosis by macrophages as spherical particles have 5,9 Besides the physicochemical properties of NMs, the macrophage phenotype also has a great impact on NM endocytosis.…”

Investigating the Role of Shape on the Biological Impact of Gold Nanoparticles in Vitro

“…Many studies have undertaken investigations into how differently shaped NPs may interact with, or be internalised by mammalian cells [19], yet in order to fully comprehend the potential of alternatively shaped GNPs for biomedical applications, their biochemical impact must also be considered [20]. However, understanding as to how the manipulation of GNP shape relates to their biocompatibility is equivocal [5,21,22].…”