Summary of TiO₂ NP-induced perturbation of metabolic pathways and their biological impact on different cells.

NP	Size [nm]	Coating	Cell	Dose/exposure time	Analytical platform	Perturbed metabolic pathway	Biological effect	Ref.
TiO2	10	N/A	RAW264.7	10, 100 μg mL−1	UPLC-MS	COX-2; PGD2, PGE2, 15 d-PGJ2 ↑	Mitochondrial dysfunction	210
			BMDM	24 h	GC-MS for 13C-labelled glutamine (flux analysis)	TCA ↓	Inflammatory response
						ATP ↓
TiO2	10–100	N/A	HaCaT	5, 50, 100 μg mL−1	GC-MS	Acetyl-CoA	Oxidative stress	206
				24 h	LC/MS/MS	GSH ↓	Mitochondrial function disruption
						Acetyl-carnitine
						Glycolysis ↓
						Pentose phosphate pathway ↓
						Nucleotide ↓
TiO2	N/A	N/A	L929	30 μg mL−1	GC-TOF-MS	Carbohydrate metabolism and TCA ↓	Metabolism changes	150
				48 h		Glycolysis ↓
						Fatty acid ↓
						Purine metabolism ↓
TiO2	5	N/A	L929	100, 200 μg mL−1	GC-TOF-MS	Carbohydrate metabolism and TCA ↓	Mitochondria damage	212
				48 h		Pentose phosphate pathway↓	Oxidative stress
						Nicotinamide metabolism block
TiO2	5	N/A	L929	100 μg mL−1	GC-TOF-MS	Amino acid ↑	Oxidative stress	213
				48 h		Carbohydrate ↑	Energy damage
						Nucleotide ↑	Inhibition of DNA and RNA synthesis
TiO2	18	N/A	HGF	0.2, 0.8, 3.2 mM + IL-β 3 ng mL−1	CE-TOF-MS	Amino acid ↓	Inflammation	215
				24 h		Urea cycle ↓
						GSH synthesis ↓
						Polyamine ↓
TiO2	8–142	N/A	HepG2	3, 30 μg mL−1	GC-MS	GSH ↓	Oxidative stress	216
				72 h	UPLC/MS/MS	Fatty acid
TiO2	21	N/A	BEAS-2B	12.5, 25 μg mL−1	LC-MS	S1P pathway ↑	Inflammation	217
				6 h		Folate cycle ↑	Oxidative stress
						Fatty acid oxidation	DNA damage
						GSH ↓
						Lipid ↑
TiO2	21	N/A	RLE-6TN	0.1, 1, 10 μg cm−2	HPLC-MS/MS	Lipids ↑	Oxidative stress	231
				24 h	FIA-MS/MS	Amino acid
						Biogenic amines
TiO2	21	N/A	RLE-6TN	1, 2.5, 5, 10, μg cm−2	HPLC-MS	Amino acid	Oxidative stress	230
			NR8383	24, 48 h		Biogenic amine
						Lipid
TiO2	21	N/A	RLE-6TN	0.1–50 μg cm−2	HPLC-MS	GSH	Oxidative stress	232
			NR8383	24, 48 h		Amino acid
						Biogenic amine
						Lipid
TiO2	42	N/A	E. coli	2.5–10 μg mL−1	GC-TOF-MS	Polyamine; putrescine ↓	Oxidative stress	233
				3 h		Amino acid; glycine ↑
TiO2	8–37	N/A	E. coli	10, 100 ppm	1H NMR	TCA ↑	Cell membrane damage	234
				3 h		Amino acid ↑	Oxidative stress
						ATP ↑
						Fatty acid ↑
						Polyamine; putrescine ↑
TiO2	30	N/A	P. polycephalum macroplasmodium	9, 15 18 mg mL−1	GC-MS	Amino acid	Oxidative stress	235
				72 h		GSH↑	ROS imbalance
						Nucleotide
						Polyamine
						Carbohydrate
TiO2/CdS/ZnS	10/30/40	N/A	Bacillus subtilis	0.1953, 3.125 mg mL−1	LC/MS	Lipid ↓	Membrane damage	236
						Biomolecules synthesis ↓	ROS generation
						ATP ↓