Table 2. Summary of Biodistribution, Toxicity, and Persistence Investigations on CuNPs.

authors	toxicity and persistence	administration
Shi et al., 2017103	100% of human type II alveolar epithelial cells were alive 4 h after the treatment for concentrations up to 50 μg/mL, while at 100 μg/mL a significant reduction was recorded.	in vitro
Zheng et al., 2017104	Viability was above 80% up to 1000 μg/mL for human mesenchymal stem cells.	in vitro
Amorim et al., 201945	Cashew gum-stabilized CuNPs on murine macrophages and murine fibroblast cells, above 80% even up to 1000 μg/mL.	in vitro
Zhou et al., 202090	CuS hydrogels after 48 h on mouse embryonic fibroblasts, above 80% even up to 1000 μg/mL.	in vitro
Yin et al., 2017109	GSH-CuNPs persisted mostly in the bladder for the first hours, with rapid clearing of the metal complex to urine.	injection
Yang et al., 2015110	78.5% ID of glutathione-CuNPs was excreted through the urine in the first 24 h, and 22% ID of the Cu(II)complexes was found in the urine. After 24 h, about 30% ID of the Cu(II)complex was in the liver and up to 0.9% ID was present in the kidneys, lowering to 0.6% ID in brain and 0.3% ID in lungs.	injection
Liang et al., 2017111	After 24 h, only 7.7% ID and 3.3% ID accumulated in liver and kidneys, respectively; also detected in the heart, slowly disappearing after 2 h.	injection
Han et al., 2019114	Ultrasmall copper selenide NPs, 10 mg/kg, are eliminated mostly in urine and feces in 6–12 h (29.2% and 36.7%, respectively). In the first 2 h, Cu2–xSe was found located mostly in the kidneys (12.1 μg/g of tissue), then decreased at 72 h (2 μg/g of tissue).	injection
Feng et al., 2015115	120 nm CuS nanoplates at a concentration of 5.5 mg/kg; levels in liver and kidneys increased to 1.6 and 0.9 μg/g at 4 h.	injection
Dey et al., 2019116	Hepatotoxicity was also found on mice orally treated with up to 6.5 mg/kg of 40–60 nm CuNPs in a diet for 4 weeks.	orally
Lei et al., 2015118	Liver damage in mice orally treated with a shorter regime but with a higher dose of NPs (5 days, 200 mg kg–1 d–1 of CuNPs).	orally
Cholewińska et al., 2018117	Accumulation of copper in the brain of mice after a 4 weeks of CuNPs diet; higher with respect to the carbonate-based diet.	orally
Fahmy et al., 2020119	Accumulation in all brain areas, except the medulla and mid brain; hippocampus contained 0.04 mg of copper per gram of tissue.	intranasal
Shi et al., 2020125	Increase in primary components of β-amyloid plaques in vitro.	in vitro
Sandhya Rani et al., 2013128	After inhalation, a certain degeneration of lungs, fibrosis, and granuloma.	inhalation