Gold Nanoparticle-Induced Cell Death and Potential Applications in Nanomedicine

Abstract

Cell death is crucial to human health and is related to various serious diseases. Therefore, generation of new cell death regulators is urgently needed for disease treatment. Nanoparticles (NPs) are now routinely used in a variety of fields, including consumer products and medicine. Exhibiting stability and ease of decoration, gold nanoparticles (GNPs) could be used in diagnosis and disease treatment. Upon entering the human body, GNPs contact human cells in the blood, targeting organs and the immune system. This property results in the disturbance of cell function and even cell death. Therefore, GNPs may act as powerful cell death regulators. However, at present, we are far from establishing a structure-activity relationship between the physicochemical properties of GNPs and cell death, and predicting GNP-induced cell death. In this review, GNPs' size, shape, and surface properties are observed to play key roles in regulating various cell death modalities and related signaling pathways. These results could guide the design of GNPs for nanomedicine.

Keywords: apoptosis; autophagy; cell death; gold nanoparticles; necrosis; proliferation.

Figure 1

Long polyethylene glycol-capped gold nanorods induced significant reactive oxygen species (ROS) production, disrupted the mitochondrial membrane potential and elicited apoptosis, while mercaptopropane sulfonate-capped gold nanospheres did not show any of cytotoxic effects. Reprinted with permission from reference [50]. Copyright (2012) American Chemical Society.

Figure 2

Surface chemistry of GNPs plays a predominant role in cell death dictation instead of size and shape. Reprinted with permission from reference [79]. Copyright (2017) American Chemical Society.

Figure 3

GNPs induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment. (A) Formation of cyan fluorescent protein (CFP)-LC3 dots (pseudocolored as green) in CFP-LC3 NRK cells treated for 24 h with 1 nM GNPs of the sizes indicated. Left, confocal image; right, bright-field image (scale bar, 10 μm). (B) Statistical analysis of the number of autophagosomes (APs) per cell after 24 h of treatment. (C) Size-dependent cellular uptake of GNPs. The graph shows the number of GNPs per cell after incubation with 1 nM GNPs for 24 h. (D) TEM images of NRK cells untreated (control) or treated with GNPs with diameters of 10, 25, and 50 nm. The GNPs are internalized by cells and trapped inside lysosomes (scale bar, 2 μm). (E) Vacuoles induced by GNP treatment are enlarged lysosomes. NRK cells were incubated for 24 h with plain medium (control) or with 1 nM GNPs. Inset: close-up of the enlarged lysosomes (scale bar, 10 μm). Adapted with permission from reference [103]. Copyright (2011) American Chemical Society.