Surface and Size Effects on Cell Interaction of Gold Nanoparticles with Both Phagocytic and Nonphagocytic Cells

Abstract

With the development of nanotechnology and its application in biomedicine, studies on the interaction between nanoparticles and cells have become increasingly important. To understand the surface and size effects on cell interaction of nanoparticles, the cellular uptake behaviors of two series of gold nanoparticles (AuNPs) with both positively and negatively charged surfaces and sizes range from ~16 to ~58 nm were investigated in both phagocytic RAW 264.7 and nonphagocytic HepG2 cells. The internalization of AuNPs was quantified by ICP-MS, and the intracellular fate of NPs was evaluated by TEM analysis. The results showed that the AuNPs with positive surface charge have much higher cell internalization ability than those with negative surface charge in nonphagocytic HepG2 cells. However, the uptake extent of negatively charged AuNPs was similar with that of the positively charged AuNPs when in phagocytic RAW 264.7 cells. Among the tested size range, negatively charged AuNPs with a diameter of ~40 nm had the highest uptake in both cells, while the positively charged AuNPs did not show a certain tendency. Intracellular TEM analysis demonstrated the different fate of AuNPs in different cells, where both the positively and negatively charged AuNPs were mainly trapped in the lysosomes in HepG2 cells, but many of them were localized in phagosomes when in RAW 264.7 cells. Cytotoxicity of these AuNPs was tested by both MTT and LDH assays, which suggested NP's toxicity is closely related to the tested cell types besides the surface and size of NPs. It demonstrates that cell interaction between nanoparticles and cells is not only affected by surface and size factors but also strongly depends on cell types.

Gold nanoparticles allow detection of early-stage edema in mice via computed tomography imaging

“…This result is different from previous data where negatively charged AuNP-MUA NP decreased cellular dehydrogenase levels on RAW 264.7 phagocytes and relatively small NPs (16 nm) revealed higher toxicity than large particles. 35 Thus, we conclude that the biocompatibility of GNPs depends not only on surface functionalization but also on the tested cell line and cell types. In agreement with data from Taylor et al who found that multiple NP properties such as size, zeta potential, and surface functionalization can determine their toxic effects on cells, 46 we conclude that AuroVist™ GNPs are nontoxic to murine macrophages, but these data may not be transferred to other GNPs exhibiting similar size or zeta potential.…”

“…52 The authors concluded that these GNPs efficiently accumulate within these cells due to opsonization. In addition, it was shown before that NPs with a higher diameter (~40 nm) and negatively charged GNPs were taken up by phagocytes in advance to positively charged or smaller NPs, 35 demonstrating that AuroVist™ 15 nm with a hydrodynamic diameter of 36 nm and a negative zeta potential might behave similarly. Consequently, it is most likely that the mCT signals of edema occur to an extent due to the uptake of negatively charged 15 nm AuroVist™ NPs into phagocytic cells from the blood stream subsequently migrating to the edema region.…”

“…In agreement with data from Taylor et al who found that multiple NP properties such as size, zeta potential, and surface functionalization can determine their toxic effects on cells, 46 we conclude that AuroVist™ GNPs are nontoxic to murine macrophages, but these data may not be transferred to other GNPs exhibiting similar size or zeta potential. Moreover, the adsorption of a protein corona to the NP, which might differ due to size or surface of the NP, 35 can affect NP uptake or interaction with the phagocytes. Consequently, each NP type exhibits different properties which can directly or indirectly impact NP biocompatibility which has to be considered when measuring cell viability.…”

“…Some studies declare them as nontoxic, 32 but some see their toxic potential 33 to depend on size, surface chemistry, and shape of the GNPs. [34][35][36][37] As a result, it was suggested that negatively charged serum protein-coated GNPs can induce cell damage through extrinsic and intrinsic apoptotic pathways. 38 In contrast to that, citrate-coated GNPs were found to have less cytotoxic and oxidative stress potential and inhibit the nitric oxide production in macrophages when coated with thiolated polyethylene glycol.…”

Biocompatible polymeric coatings do not inherently reducethe cytotoxicity of iron oxide nanoparticles

“…However, as shown in the study by Petri-Fink et al (2005), due to the interaction of the amino groups on the surface of CS with the negatively charged domains on cell membranes, CS-IONPs pass through the cell membrane. Cationic NPs were shown to have enhanced cellular uptake compared to anionic or neutral NPs and to induce more ROS and mitochondrial and lysosomal damage (Mahmoudi et al, 2011a;Liu et al, 2013;Calatayud et al, 2014). They were also shown to cause more disruption of plasma membrane integrity and more hole formation, particularly in nonphagocytic cells (Nafee et al, 2009;Frohlich, 2012;Carvalho et al, 2016).…”