Recent studies highlighting the influence of the physicochemical properties of NPs on their cellular uptake and cytotoxicity.

Property	Parameter	NPs	Cell lines	Uptake mechanism	Cytotoxicity	Highlights	Ref.
Size	(5 and 200 nm)	TiO2	A549	—	ROS generation ↑	Smaller primary-sized NPs are more cytotoxic	38
	(10 and 50 nm)	Al2O3			Nutrient depletion
Size	10, 40, 75 nm	Ag	BEAS-2B	Clathrin, caveolin/lipid raft, macropinocytosis and phagocytosis	Ag release (Trojan horse)	10 nm NPs are the most cytotoxic	68
					DNA damage
Size	Spheres (15 nm-NP1, 45 nm-NP2, and 80 nm-NP3), rods (33 × 10 nm-NR), stars (15 nm-NS)	Au	SMCC-7721	Endocytosis (depends on corona)	Cell viability ↓	NS and NR are much more cytotoxic than the three spherical Au NPs. Cellular uptake in the order NP3 > NR > NP2 ≳ NP1 ∼ NS	88
Shape			GES-1
Corona			4T1
Size	Spheres (different sizes and coating), cubes, rods, prisms	Au	PC3	Endocytosis	Membrane damage	Increased uptake of smaller particles. AuNS are the most cytotoxic, followed by AuNPr, while both AuNR and AuNC are not toxic	89
Shape					Cell death
Corona
Size	Spheres (10 nm), flowers (370 nm), rods (41 nm), prisms (160 nm), stars (∼240 nm)	Au	HeLa	Endocytosis	Cell viability ↓	Au nanospheres and nanorods are more cytotoxic than star, flower and prism AuNPs	70
Shape			HEK293T
Shape	Rods (L = 39 nm, W = 18 nm), stars (215 nm), spheres (6.3 nm)	Au	hFOB 1.19	Endocytosis & phagocytosis	Mitochondrial dysfunction	Au nanostars are the most cytotoxic to the three cell lines while AuNPs spheres are the least cytotoxic	90
			143B		Membrane damage, apoptosis
			MG63
			hTERT-HPNE
Shape	Spherical and needle-like	PLGA–PEG	HepG2	Endocytosis	DNA damage, membrane damage, apoptosis	Spherical NPs have higher cellular uptake while needle-like NPs have greater cytotoxicity	91
			HeLa
Shape	Rods	Al2O3	Rat ASTs	Phagocytosis	ROS generation, inflammatory response, metabolism changes, apoptosis	Nanorods have significantly greater cytotoxicity than nanoflakes against rat astrocytes	92
	Flakes
Surface charge	Positive, negative, neutral	Au	HaCaT	Endocytosis	ROS generation, oxidative stress, mitochondrial stress, apoptosis, or necrosis	All three NPs generated significant ROS levels, but only charged NPs caused mitochondrial stress. Charged NPs caused cell death through apoptosis, while neutral NPs caused it through necrosis	77
Surface charge	Positive & negative with different zeta potentials	Polymeric	L929	—	Cell viability ↓	Cationic NPs are more cytotoxic that anionic NPS.	84
						As absolute zeta potential increases, cytotoxicity increases
Surface charge	Positive/negative charge density and different hydrophobicity	Au	A549	Endocytosis	ROS generation	Positive trend in the cytotoxicity of NPs over their surface hydrophobicity	82
Hydrophobicity			HEK293		Apoptosis
Hydrophobicity	Three dicationic amphiphile-stabilized	Au	A549	—	ROS generation	Positive trend in the cytotoxicity of NPs over their surface hydrophobicity	81
	AuNPs				Apoptosis