Table 2.

In vitro and in vivo toxicity of AuNPs

Nanoparticles/composites	Size	Surface coating	Dosage rate and exposure time	Model (cells/animals)	Comments on toxicity (effect on cells, organs, tissues/cell viability)	References
Nanospheres	2 nm	—	0.38–3 × 10−6  m; 1, 2.5, 6, 24 h	COS‐1	Cationic particles are moderately toxic, whereas anionic particles are nontoxic facilitated by their strong electrostatic attraction to the negatively charged bilayer	[ 229 ]
Nanorods	4 nm	Chitosan on the surface	50 µg mL−1, 24 h	Mice	Improved in vitro cellular uptake and minimal toxic effects were observed	[ 230 ]
Bifunctional Au/Ni NRs	20 µm long and 170 nm in diameter	—	44 mg mL−1 4 h	HEK293	Reduced risk of cytotoxicity and immunogenicity.	[ 231 ]
Nanospheres	3.5 ± 0.7 nm	—	10, 25, 50, and 100 × 10−6 m 24, 48, and 72 h	RAW264.7	Au NPs are not cytotoxic, reduce the production of reactive oxygen and nitrite species, and do not elicit secretion of proinflammatory cytokines TNF‐α and IL1‐β, making them suitable candidates for nanomedicine.	[ 232 ]
Nanospheres	2, 10, 25, 40, 50, 70, 80, and 90 nm	Herceptin physical adsorption	10 µg mL−1 3 h	SK‐BR‐3, SNB‐19, and HeLa cells	Gold and silver NPs coated with antibodies can regulate the process of membrane receptor internalization	[ 233 ]
Nanoshperes	50 and 100 nm	Tiopronin	1 nmol L−1 3–24 h	MCF‐7	Optimal smaller size for NPs that maximizes their effective accumulation in tumor tissue.	[ 234 ]
Nanospheres	4, 12, and 17 nm	L‐cysteine	10 × 10−9 m 3 h	HeLa	Both the uptake and unbinding force values are dependent upon the size of gold NPs.	[ 235 ]
Nanorods		CTAB, PEG‐SH	0.01–0.5 × 10−3 m 24 h: In vitro (0.5–0.9 × 10−3 m in vivo) 0.5, 3, 6, 12, 24, and 72 h: In vivo	HeLa/mice	PEG‐modified gold NPs showed a nearly neutral surface and had little cytotoxicity in vitro. Following intravenous injection into mice, 54% of injected PEG‐modified gold NPs were found in blood at 0.5 h after intravenous injection, whereas most of gold was detected in the liver in the case of original gold NRs stabilized with CTAB.	[ 236 ]
Nanostars	110 10 nm	GNS SiO2/Au	10 mg g−1 4 h, 1, 4, 7, 14, 21, 28 d	Mice IV;	The mass of gold in the tissue samples ranged from our determination limit (about 70 pg) to a few micrograms.	[ 237 ]
Nanowires	0.58, 1.8, 4.5, 8.6 nm_X 200 nm	Thiols with amino, alkyl, or carboxyl end groups, serum	103–106 particles mL−1, 24 h	NIH 3T3	Internalized nanowires with high aspect ratios are more toxic to cells than nanowires with low aspect ratios.	[ 238 ]
Nanoclusters	0.8, 1.2, 1.4, 1.8, CG‐15	Triphenylphosphine	1–10 000 × 10−6  m 6, 12, 18, 24 h	HeLa Sk‐Mel‐28 L929 J774A1	Gold particles 15 nm in size and Tauredon (gold thiomalate) are nontoxic at up to 60‐fold and 100‐fold higher concentrations, respectively. The cellular response is size‐dependent, in that 1.4 nm particles cause predominantly rapid cell death by necrosis within 12 h while closely related particles 1.2 nm in diameter effect predominantly programmed cell death by apoptosis.	[ 194 ]
Nanoclsuters	1.4 nm	—	Mice: 57 mg, Rat: 285 mg Mice: 2, 4, 24 h Rat: 3, 7, 10 d	Mice, Rat	clusters reach a polydentate ligand sphere that increases the kinetic stability by orders of magnitude	[ 195 ]
Nanoparticles	12.5 nm	—	IP; 40, 200, 400 mg kg−1 day−1 8 d	Mice	AuNPs are able to cross the blood–brain barrier and accumulate in the neural tissue. Importantly, no evidence of toxicity was observed in any of the diverse studies performed, including survival, behavior, animal weight, organ morphology, blood biochemistry and tissue histology.	[ 239 ]