Morphological and Physicochemical Characterization of Agglomerates of Titanium Dioxide Nanoparticles in Cell Culture Media

Table 2

Biological effects of TiO₂ NPs with different morphological and physicochemical characteristics in in vitro and in vivo systems.

	Used nanoparticle	Geometry and size	Suspension media	Nanoparticle; concentration/dose	Model	Toxicity effects	Reference
In vitro	TiO2 NP	Nanobelts; TiO2  length was 7 μm, width was 0.2 μm, and thickness was 0.01	7.5% BSA in DPBS was added to make a 5 mg/mL suspension	10 µg/mL and 100 µg/mL	Caco-2/HT 29-MTX	THP-1 cells indicated TiO2-NB regulation of pathways associated with inflammation, apoptosis, cell cycle arrest, DNA replication stress, and genomic instability,	[37]
	TiO2 NP	Spheres; TiO2 NP is 7 nm	H2O and DMEM + 10% SFB	500 g/mL	A549 cells and NIH-3T3 cells spheroids	TiO2 NP caused the metabolic activity of the A549 cells in spheroids increase up to 350% higher	[38]
	TiO2 NP	~20–25 nm for TiO2, and rod-like 5–10 × 50–200 nm, potential −11 mV for TiO2	Pepsin, pancreatin and bile salts, PBS, DMEM	10 μg/cm^2	C2BBe1, a clone of Caco-2 cells	TiO2 were not found to be toxic, but they could be internalized by the epithelial cells as nanoparticles and may subsequently enter the circulation and migrate to other parts of the body	[39]
	TiO2 NP	Nanobelts; lengths from 5–9 μm and widths between 60 and 140 nm	Lavage fluid	50 μg/m	C57BL/6 and BALB/c and IL-1R null; mice	Carboxylation, but not humic acid modification of TNB, reduces but does not totally eliminate bioactivity of TNB, which is consistent with previous studies of other long aspect ratio nanomaterials such as carbon nanotubes	[40]
	TiO2 NP	Nanobelts and nanotubes	RPMI and DMEM with 10% FBS	10 µg/m–100 µg/mL	Caco-2/HT 29-MTX, THP-1	THP-1 cells indicated TiO2-NB regulation of pathways associated with inflammation, apoptosis, cell cycle arrest, DNA replication stress, and genomic instability	[37]
In vivo	TiO2 NP	Spheres 20 nm–250 nm	BALF	1 mg/kg	Rat and ICR mice lungs	NP mainly deposit in the alveolar region, with approximately 50% and only ~15% of this particle size depositing in tracheobronchial and nasopharyngeal regions, resulting in the influx of PMNs into the alveolar space and a large acute pulmonary inflammatory reaction	[41]
	TiO2 NP	Nanorods	BALF	1 and 5 mg/kg	Wistar; rats	Inflammation responses significantly increased neutrophilic inflammation and whole blood significantly reduced platelets and elevated numbers of monocytes and granulocytes	[42]
	TiO2 NP	Nanospheres, short belts (1–5 μm), long nanobelts (4–12 μm)	BALF	0–30 μg	Mice	Lung deposition of 135 μg TiO2. At 112 days after exposure, the lung burden was significantly lower in nanosphere-exposed mice than in nanobelt-exposed mice	[43]
	TiO2 NP	Nanobelts 1–5 μm long, with widths between 40 and 120 nm, potentials: −12.4 mV (NS), −12.5 mV (NB1), and −9.35 mV (NB2)	10 M; sodium hydroxide aqueous and albumin	30 µg NB, 7.5–30 µg	Mice	Accumulation of NBs in the interstitium of the bronchioloalveolar junction and dilated lymphatics containing intraendothelial NBs were occasionally observed. TiO2 NP shape and length affect pulmonary responses. Only the NBs caused development of pulmonary fibrosis, which correlated with the severity of pulmonary inflammation	[44]
	TiO2 NP	Short (<5 mum) and long (>15 mum) nanobelts	Ethanol; PBS/3.5% BSA; solution	Medium (DM), which is PBS containing 0.6 mg/mL mouse serum albumin and 0.01 mg/mL 1,2-dipalmitoyl-sn-glycero-3-phosphocholine	C57BL/6; Mice	Any modification of a nanomaterial, resulting in a wire, fibre, belt, or tube, is tested for pathogenic potential	[45]