Table 2.

Physicochemical properties of inhaled NPs are critial factor to cause pathobiological processes.

Nanoparticles	In Vivo Exposure Procedure (Dose, Period, Animal Model)	Physicochemical Properties	Lung Injury and Lung Disease	Ref.
MWCNT	intratracheal instillation once a day for two consecutive days; 0.6 mg/rat; 30 days; SH rat	Length	Long MWCNTs (20–50 μm) but not short MWCNTs (0.5–2 μm) exhibit increased fibroblast proliferation, collagen deposition and granuloma formation in lung tissue.	[33]
	instillation 100 µg/mice; 1, 7, 30, 90, o r 180 days; Male Balb/c mice	Suface modification NT1: none NT2: carboxylic polyacid polymer NT3: polystyrene polybutadiene polymethylacrylate(PMMA) Surface area NT1: 227. 54 m2/g NT2: 54.1 m2/g NT3: 34 m2/g	NT1 and NT2, not NT3, induced inflammatory response and these effects were observed 24 h post-instillation and lasted up to 1 month.	[55]
	intratracheal instillation(single); 2 mg/rat; 3 days; female wistar rats	Thickness (diameter) MWCNT9.4: 9.4 ± 0.3 nm MWCNT70: 70 ± 2 nm	Thin MWCNTs induced an inflammatory lung response when instilled in rats. Conversely, thick MWCNTs appeared to be of low toxicity.	[59]
Graphene	intratracheal instillation (single); 50 μg/mouse; 21 days; C57BL/6 mice	Surface modification (covalent oxidation) aggregation	GO increased the rate of mitochondrial respiration and the generation of ROS, activating inflammation.	[41]
Nickel nanowires	Pharyngeal aspiration; 7 days; 50 mg/mice; female C57BL/6 mice	Length Long: 24 ± 7 µmShort: 4.3 ± 1 µm	Long nanowires led to a moderate inflammatory response and a strong granulomatous response in the peripheral airways, but short ones did not cause these responses.	[60]
Nano-TiO2	nose-only exposure for 6 h; 20 mg/m3; 16 h; Rats	Agglomeration state: Large agglomerate (LA): >100 nm Small agglomerate (SA): <100 nm Size: 5 nm 10–30 nm 50 nm	5 nm SA particles caused a noted increase in cytotoxic effects, while oxidative damage was less compared to 10–30 and 50 nm SA particles. In SA and LA aerosols, the 10–30 nm TiO2 NP induced the most marked pro-inflammatory effects.	[61]
	Intratracheal instillation(single); 1 or 5 mg/kg; 24 h, 1 week, 1 month, and 3 months; Male rats	Surface area: (1) Nanoscale rods Dlong = 92–233 nm Dwide = 20–35 nm 26.5 m2/g (2) Nanoscale dots: 5.8–6.1 nm spherical 169.4 m2/g	No significant difference in pulmonary inflammation for long-term exposure.	[62]