Toxicity and cellular uptake of gold nanoparticles: what we have learned so far?

Abstract

Gold nanoparticles have attracted enormous scientific and technological interest due to their ease of synthesis, chemical stability, and unique optical properties. Proof-of-concept studies demonstrate their biomedical applications in chemical sensing, biological imaging, drug delivery, and cancer treatment. Knowledge about their potential toxicity and health impact is essential before these nanomaterials can be used in real clinical settings. Furthermore, the underlying interactions of these nanomaterials with physiological fluids is a key feature of understanding their biological impact, and these interactions can perhaps be exploited to mitigate unwanted toxic effects. In this Perspective we discuss recent results that address the toxicity of gold nanoparticles both in vitro and in vivo, and we provide some experimental recommendations for future research at the interface of nanotechnology and biological systems.

Fig. 1

Gold nanorods of different aspect ratios have different colors and tunable ultraviolet–visible–near-infrared spectra. Scale bars in the transmission electron micrographs at the top are 100 nm

Fig. 2

Schematic showing the physical events that occur as a result of satisfying the localized surface plasmon resonance condition, with the corresponding applications. See text for details

Fig. 3

(Upper panel): Cartoon demonstrating the formation of protein corona on a gold nanoparticle surface. Adsorption of serum proteins onto the surface of gold nanoparticles flips their effective surface charge. (Lower panel): Effective surface charge (zeta potential) of gold nanorods capped with cetyltrimethylammonium bromide, CTAB (white bars) and poly(acrylic acid), PAA (black bars). In aqueous solution, CTAB-capped gold nanorods have a positive effective surface charge and PAA-coated nanorods are negative. However, both have the same negative effective surface charge after they mixed with serum proteins and subsequently purified

Fig. 4

“The supernatant control”. A gold nanorod solution is exposed to cells, and in this cartoon kills 70% of the cells at a certain dose. An identical gold nanorod solution is centrifuged, and the colorless supernatant exposed to cells. The similar toxicity of both solutions indicates that the nanoparticles are not toxic by themselves, but small molecules (leftover reagents, or desorbed capping agents) are

Fig. 5

Left: average lifespan of mice receiving gold nanoparticles, 8–37 nm in diameter, was shortened compared to smaller and larger nanoparticle sizes. The break marks on the top of bars indicate that no death was observed during the experimental period. Right: MTT assay for the same gold nanoparticles using the HeLa cell line. Images reproduced with permission from (Chen et al. 2009). Copyright: Springer Science

Fig. 6

Cartoon demonstrates the concept of the biodegradable plasmon-resonant liposomes. The whole composite absorbs in the near-infrared region and thus serve as “nanoheaters” to destroy cancer cells. Upon disruption of the carrier (liposomes), the nanoparticles could be released and have a higher chance to be bio-eliminated