Table 2.

SiO₂ nanotoxicology

Type	Crystal phase	Size and characteristics	Animal or cell type	Concentration	Assay	Results	Reference
1 Mesoporous SiO2	Amorphous	130 nm by SEM, TEM Amine and phosphate functionalized Hexagonal and 2 nm pores	Cancer cells (e.g. PANC-1, AsPC-1)	6.4, 64 mg/mL, 6.4, 64 g/mL 1 day	In vitro bioassays WST assay Apoptosis assay Necrosis assay	Non-toxic without cancer agent camptothecin Toxic to cancer cells with cancer agent	Lu et al. (2007b)
2 Mesoporous and luminescent SiO2	Amorphous	100–120 nm by TEM 780–1050 m2/g surface area Rhodamine B incorporated Hexagonal and 2–3 nm pores (+) and (-) charged surfaces	Adipocytes (3T3-L1) Human mesenchymal stem cells (hMSCs)	0.1 mg/mL, 3 h (cytotoxicity) 0.1 mg/mL, 1 day (proliferation)	In vitro bioassays • MTT assay	Non-toxic regardless of surface charge Adipogenic and osteogenic differentiation unaffected Uptake efficient regardgless of surface charge	Chung et al. (2007)
3 Multifunctional and luminescent SiO2	Amorphous	sub-50 nm by SEM, TEM Amine/carboxylate/Gadolinium functionalized Luminescent (Ru(bipy)32+)	Monocyte cell (bone marrow progenitor cells from C57BL/6 mice)	0.012, 0.123, 1.23, 12.3, 123 μg/5000 cells 1 day	In vitro bioassays • Cell viability assay	• Non-toxic	Rieter et al. (2007a,b)
4 Polymer and protein functionalized luminescent SiO2	Amorphous	20 nm by TEM Luminescent (Ru(bipy)32+) Polymer and protein coated	Jarkat T luekemia cell	Concentration enough for fluorescence microscopy 1, 3, 6h	In vitro bioassays Necrosis assay Apoptosis assay	Non-toxic Apoptotic, necrotic profile same as nontreated	Bottini et al. (2007)
5 Organically modified SiO2	Amorphous	20 nm by TEM Porphyrin incorporating ORMOSIL	Tumor cells (e.g. Colon-26, RIF-1)	0.5 μM/well 0–8 J/cm2 irradiation	In vitro bioassays • Photosensitization assay	Non-toxic without light Toxic to tumor cells with increasing light dosage	Ohulchanskyy et al. (2007)
6 Silicon nanowires	Silicon	90 nm in diameter 6 μm height	Murine embryonic stem cell Kidney cell (HEK293T)	N/A (grown on Si wafer) Several days	In vitro bioassays • Cell incubation	• Murine stem cells survive for several days interfaced to silicon nanowires with 100 nm diameter	Kim et al. (2007c)
7 Synthetic SiO2	Amorphous	SiO2 from Na2SiO3 15–25 nm (SEM)/177–200 nm (DLS) SiO2 from TEOS 65–95 nm (SEM)/230–243 nm (DLS) SiO2-chitosan composite 10–15 nm (SEM)/153–177 nm (DLS)	Fibroblast cells Epithelial cells	0.21–0.667 mg/mL for 2 days	In vitro bioassays MTT assay LDH assay	SiO2-chitosan composite has less toxicity Silica is more lethal to fibroblast cells Longer the cell doubling time, the more cytotoxic	Chang et al. (2007)
8 Silica shell with quantum dot core	Amorphous shell CdSe/ZnS core Amine termination	• 15–20 nm overall size	Leukemia cells (Jurkat, K-562) Lymphocytes	5 μM QD core concentration 0.5, 3, 24, 48 h 5 × 105 cell/well	In vitro bioassays • Flow cytometry	Non-toxic up to 5 μM QD core concentration, 2 day, no light exposure Slightly cytotoxic with UV irradiation (ROS, radical generation probable) Intracellular delivery possible	Zhelev et al. (2006)
9 Multifunctional silica nanotubes	Amorphous walls	50 nm diameter 200 and 500 nm lengths No surface modification Magnetite incorporated and amine functionalized (+ charge)	Human metastatic breast cancer cell (MDA-MB-231) Normal human umbilical vein endothelial cells	• 0.005, 0.05, 0.5, 5 μg/mL	In vitro bioassays • MTT assay	Non-toxic only at low concentrations (below 0.5 μg/mL) Toxicity is length independent but dose-dependent (+) Charged 200 nm long SiO2 nanotubes are toxic, especially for normal cell lines	Son et al. (2006)
10 Flame engineered SiO2	Amorphous Crystalline	14 nm	Human mesothelioma rodent fibroblast cell lines (3T3)	15 ppm for 6 days	In vitro bioassays MTT assay Total DNA measurement DNA Hoechst assay	Non-toxic	Brunner et al. (2006)
11 N/A	Amorphous	0.5–4 μm/1–12 μm	Human leukemic monocyte lymphoma (U937) used differentiated	0.125–1 mg/well	In vitro bioassays • LDH assay	SiO2 particles are the most toxic SiO2 > metal alloy > Al2O3 > TiO2	Yoshida et al. (2003)
12 15 nm SiO2 46 nm SiO2 Crystalline (Min-U-Sil 5) (Min-U-Sil 5)	Amorphous (15, 46 nm) Crystalline (Min-U-Sil 5)	15 nm SiO2 (15 ± 5 nm) 46 nm SiO2 (46 ± 12 nm) Min-U-Sil 5 (629 ± 272 nm)	Human lung cancer cells (A549)	10, 50, 100 μg/mL for 48 h for GSH, MDA, and LDH (1 × 104 cell/well; T75) 10, 50, 100 μg/mL for 48 h for SRB (1 × 104 cell/well; 24 well) 48 h for ROS	In vitro bioassays Sulforhodamine B assay LDH assay Intercellular ROS GSH measurement MDA measurement Protein assay	15, 46 nm SiO2 particles are toxic which is dose-dependent and time-dependent at 10–100 μg/mL Amorphous was more toxic than crystalline SiO2 for cultures involving human bronchoalveolar carcinoma-derived cells	Lin et al. (2006a)