Table 1 In vivo toxicological studies of NPs mediated autophagy
From: Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine
NPs | Size (nm) | Coating | Animal model | Administration | Dose (mg/kg BW) | Exposure time | Organ toxicity | Autophagy alterations | References |
|---|---|---|---|---|---|---|---|---|---|
TiO2 NPs | 19.3 ± 5.4 | bare | A/J Jms Slc mice (5 weeks old) | inhalation | 2.5,5.0,10.0 (mg/m3) | 6 h per day for 4 weeks | 1. hyperplasia and hemorrhage 2. inflammatory response in the lung | induction of autophagy LC3 ↑ Beclin 1 ↑ | [79] |
Cd-based QDs | 12 | bare | male Balb/c mice | tail vein | 0.1 ~ 0.3 nmol | 24 h | 1. increase of aspartate transaminase and glutamate pyruvate transaminase 2. haemocytes and necrosis in the live and kidney | stimulated autophagic flux LC3 ↑ P62 ↓ | [80] |
ZnO NPs | 47.8 | bare | Female Balb/c mice (8 weeks old) | Intraperitoneal or intravenous injection | 10 | once per week for 4 weeks | increase in serum creatinine and BUN in the kidney | autophagy induction autophagosome accumulation, LC3 ↑ | [81] |
200–250 | bare | Balb/c mice (6–8 weeks old) | oral gavage | 200, 500 | 6 days | massive infiltration of inflammatory cells and DNA damage in the liver | autophagy induction autophagosome accumulation | [82] | |
UCNs | < 200 | bare | male C57BL/6 J mice (6–8 weeks old) | tail vein | 100 | 24 h | 1. inflammatory cell infiltrates 2. ALT levels increased in the liver | induction of autophagy autophagosomes accumulation LC3 ↑ LAMP ↑ | [83] |
PAMAM NPs | 5 ~ 6 | bare | female Balb/c mice (6–8 weeks old) | intraperitoneal injection | 100 | 10 days | 1. hepatocytic necrosis and vacuolization 2. weight decreased 3. ALT and AST increased in the liver | induction of autophagy accumulation of vacuolization LC3 ↑ | [84] |
Graphene nanoplatelets | 3 ~ 4 | bare | ICR mice 6 Weeks old) | intratracheal instillation | 2.5, 5 | 1, 7, 14, and 28 days | 1. hyperplasia and hemorrhage 2. inflammatory response in the lung | blockade of autophaic flux LC3 ↑ P62 ↑ | [85] |
PAMAM NPs | _ | bare | male Balb/c mice (6–10 weeks old) | intratracheal administration | 50 | 24 h | lung inflammation and changed the lung elastance | induction of autophagy LC3 ↑ | [86] |
SWCNTs | – | COOH-CNT PABS-CNT PEG-CNT | male Balb/c mice(6–8 weeks old) | intratracheal administration | 15 | 24 h | 1. Acute pulmonary inflammation 2. severe lung edema | induction of autophagy autophagosomes accumulation LC3↑ | [87] |
CdTe QDs | 4.08 | bare | male Balb/c mice (8–10 weeks old) | intravenous injection | 8 and 16 nmol/kg | 24 h | 1. increase in uric acid, creatinine and BUN 2. UPR and ER-phagy in the kidney and liver | induction of autophagy LC3↑ | [88] |
Fe3O4 NPs | 15 ~ 20 | PLGA | NIH mice | intraperitoneal injection | 10 | 2, 4, 8, 10 and 12 days | extensive accumulation of autophagosome in the kidney and spleen | induction of autophagy autophagosomes accumulation LC3 ↑ | [89] |
MWCNTs | 10 ~ 12 | bare | male Wistar rats (200–220 g) | intraperitoneal injection | 2.5 | once per day for 14 days | decrease in hippocampal synaptic plasticity and spatial cognition in the brain | induction of autophagy LC3 ↑ Becline ↑ | [90] |
CoCr NPs | 80 ± 14.6 | bare | C57BL/6 mice (12 weeks old) | intravenous injection | 0.12 mg per mouse | 9.5, 12.5 days of pregnancy | 1. increase in GFAP in hippocampus; 2. release IL-6 and DNA injury in the brain | blockade of autophaic flux LC3 ↑ P62 ↑ | [91] |
SiNPs | 62 | bare | Male and female ICR mice (8 weeks old) | intravenous injection | 29.5, 103.5 and 177.5 | 14 ays | 1.inhibitory effect on the expression of ICAM-1 and VCAM-1 2. impair angiogenesis | induction of autophagy LC3 ↑ | [92] |