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Table 1 Working mechanism and applications of NMs in neurological diseases

From: Nanomaterials alleviating redox stress in neurological diseases: mechanisms and applications

NMs

Characterization

Disease models

Treatment

Target RONS

Valence states

Working mechanism

Results

Refs.

Fe3O4 NPs

Size: 20 nm

AD

In vivo: 6-week-old drosophila AD model

In vitro: PC12 cells

200 μg/mL, fed with food containing NPs

H2O2

–

CAT-like activity for ROS scavenging

Diminish the α-Synuclein accumulation, enhance climbing ability and prolong life span of animals

[34]

Fe3O4 NPs

Size: 200 nm; Surface modification: rough surface with PEG

Ischemic stroke

In vivo: 8-week-old male mice MACO models

In vitro: PC12 cells

15 and 50 mg/kg, orally administered

H2O2, ·OH, O2·−

–

CAT-, POD-, SOD-like activity for ROS scavenging and protecting the BBB integrity

Reduce cerebral infarct volume and improve the symptoms of neural dysfunction

[9]

CeO2 NPs

Size: 10 nm

Ischemic stroke

In vivo: hippocampal brain slice of 2 ~ 5-month-old CD1 mice

0.1–2 μg/mL, added to the solution with brain slices

O2·−, ONOO−, ·NO

–

SOD-like activity for RONS scavenging

Reduce the area of ischemia-induced cell death

[51]

CeO2 NPs

Size: ~ 3–8 nm

AD

In vitro: cortical neurons cultured with Aβ peptide

100 nM for 3 h

ONOO−

Ce3+ and Ce4+

Scavenging ONOO− and reducing Aβ-induced mitochondrial fragmentation

Reduce the neuronal cell death

[54]

CeO2 NPs

Size: ~ 20 ± 5 nm; Shape: polyhedral; Surface modification: ZIF-capped

Ischemic stroke

In vivo: female SD mice MACO models

In vitro: PC12 cells

0.2 and 0.4 mg/kg, tail intravenously administered for 3 d

H2O2, ·OH, O2·−

Ce3+ and Ce4+

ROS scavenging and anti-neuroinflammation

Block ischemic reperfusion damage and reduce the infarct volume

[28]

CeO2 NPs

Size: 3 nm; Surface modification: aminocaproic acid

SAH

In vivo: male SD rats SAH model

In vitro: RAW264.7

0.5 mg/kg, intravenously administered at 1 h post-SAH

O2·−

Ce3+ and Ce4+

ROS scavenging and anti-neuroinflammation

Reduce the neuronal death and the brain edema

[8]

CeO2 NPs

Size: 4.3 ± 0.5 nm; Shape: spherical; Surface modification: Angiopep-2 and PEG

Ischemic stroke

In vivo: SD rats MACO models

In vitro: BCECs

0.5 mg/kg, tail intravenously administered for 24 h

H2O2, ·OH, O2·−, ·NO

Ce3+ and Ce4+

ROS scavenging and protecting BCECs

Prevent the BBB damage and reduce the infarct volume

[10]

CeO2 NPs

Size: 3–4 nm; Shape: spherical; Surface modification: PEG

ICH

In vivo: 8-week-old male SD rats ICH models

In vitro: U937 and RAW264.7 cells

0.5 mg/kg, intravenously administered for 6 and 30 h

H2O2, ·OH, O2·−, ONOO−, ·NO

Ce3+ and Ce4+

RONS scavenging, anti-neuroinflammation and reducing microglia recruitment

Reduce the brain edema

[47]

Cr-doped CeO2 NPs

Size: 8–12 nm

TBI

In vivo: 8–10-week-old male C57BL/6 mice TBI models

Nanozyme patch adhered to the injured brain area for 2–28 d

H2O2, ·OH, O2·−, ONOO−, ·NO

Ce3+ and Ce4+

RONS scavenging and anti-neuroinflammation

Reduce the neuronal cell death and promote wound healing

[48]

CeO2 NPs

Size: 3, 11, 22 nm; Surface modification: lipid, PEG, and TPP

PD

In vivo: C57BL/6 mice injected with MPTP

In vitro: SH-SY5Y and HeLa cells

0.1 and 0.3 mM, stereotactically administered for 7 d

-

Ce3+ and Ce4+

Scavenging intracellular and/or mtROS and anti-neuroinflammation

Protect axons of dopaminergic neurons and reduce activation of microglia

[46]

Single-atom Pt-CeO2

CeO2 clusters doped Pt

TBI

In vivo: male C57BL/6 mice TBI models

In vitro: HT22 cells

Nanozyme bandage pasted on injured brain area for 12 and 26 d

·OH, O2·−, ONOO−, ·NO

Ce3+ and Ce4+

RONS scavenging and anti-neuroinflammation

Improve impaired neurocognition

[166]

TPP-CeO2 NPs

Size: 22 nm; Surface modification: PEG and TPP

AD

In vivo: 6-month-old 5XFAD transgenic mice AD models

In vitro: SH-SY5Y cells

Stereotaxically administered for 7 d

H2O2, O2·−

Ce3+ and Ce4+

Scavenging mtROS and inhibiting microglia activation

Mitigate the reactive gliosis and reduce the neuronal cell death

[45]

CuO and Cu2O NP clusters

Size: 65 ± 7 nm; Surface modification: tyrosine, aspartic acid, glutamic acid, and phenylalanine

PD

In vivo: 8–10-week-old male C57BL/6 mice injected with MPTP

In vitro: SH-SY5Y cells cultured with MPP+

0.2 mg/mL, stereotaxically administered for 15 d

H2O2, ·OH, O2·−

–

CAT-, SOD-, POD-, and GPx- like activity for ROS scavenging

Promote the cognitive recovery and rescue the memory loss

[31]

Mn3O4 NPs

Size: cubes: 50 nm, polyhedron: 60 nm, hexagonal plates: 140 nm, flakes-like morphology: 100 nm, and flower-like morphology: 180 nm

PD

In vitro: SH-SY5Y cells cultured with MPP+

2.5, 5, 10, 20 ng/μL

H2O2, ·OH, O2·−

–

CAT-, SOD-, and GPx- like activity for ROS scavenging

Rescue the loss of neurites

[59]

2D vanadium carbide MXenzyme

Lateral size: several micrometers; Shape: 2D nanoflakes

PD

In vivo: 6-week-old female C57BL/6 mice injected with MPTP

In vitro: L929 and PC12 cells

10 mg/mL, 4 μL, unilaterally injected into the striatum

H2O2, ·OH, O2·−

V5+ and V4+

CAT-, SOD-, POD-, and GPx-like activity for ROS scavenging, anti-neuroinflammation, and inhibiting microglia activation

Increase the TH levels and reduce the lipid peroxidation

[66]

Mo-based POM nanoclusters

Size: ~ 1 nm

Ischemic stroke

In vivo: MCAO rats

In vitro: primary neurons

1 μg/μL, 50 μL, intrathecally administered

H2O2, ·OH, O2·−

–

RONS scavenging and anti-neuroinflammation

Reduce the infarct volume and improve the neurological function

[77]

MoS2 NPs

Size: ~ 100 nm; Shape: spherical

AD

In vitro: SY5Y cells cultured with Aβ42

1, 5, 10 μg/mL for 12 h

–

–

ROS scavenging and inhibiting Aβ aggregation

Reduce the neuronal cell death

[76]

CuxO@EM-K

Size: 90 ± 15 nm; Surface modification: DSPE-PEG

AD

In vivo: 9-month-old female 3xTg-AD mice models

15 mg Cu/kg, intravenously administered for 12, 24, 36, and 48 h

H2O2, O2·−

–

ROS scavenging and adsorbing Aβ

Reduce the Aβ burden in the blood and brain and ameliorate memory deficit

[73]

Pt NPs

Size: 2–3 nm

Ischemic stroke

In vivo: male C57/BL6 mice MACO models

4.0 μM/kg, 0.3 mL, tail intravenously administered

O2·−

-

ROS scavenging

Reduce the infarct volume and improve motor function

[86]

Pd hydride NPs

Size: ~ 30 nm; Shape: cubic

AD

In vivo: male and female 5-month-old 3xTg-AD mice models

In vitro: Neuro-2A and N2a-SW cells

0.5, 1, and 2 mg/mL, 2 μL, bilateral intracerebral administered

·OH

–

ROS scavenging and ameliorating the mitochondrial dysfunction

Ameliorate the cognitive impairment, reverse the synaptic deficits and neuronal death, and inhibit Aβ generation and aggregation

[88]

PEG-HCCs

Size: 40 nm × 2 nm; Surface modification: PEG

Ischemic stroke

In vivo: male SD MACO rat

In vitro: B. End3 brain endothelial cells and E17 primary cortical neurons

4 mg/kg, < 0.1 mL, tail intravenously administered

H2O2, ·OH, O2·−

–

ROS scavenging

Reduce the infarct volume, hemisphere swelling, and hemorrhage score, and improve neurological function

[94]

Carboxyfullerene

–

PD

In vivo: male macaque fascicularis monkey; MPTP-induced PD model; Age (years old): controls: 7.6 ± 2.2; experimental group: 8.1 ± 2.3

200 mg/mL, 3 mg/kg/day for 8 weeks, parenteral administered

–

 

Alleviating redox stress and anti-neuroinflammation

Reduce striatal injury, improved parkinsonian motor ratings, and increase the striatal dopamine levels

[7]

Polyhydroxylated fullerene derivatives

–

Ischemic stroke

In vivo: 10–12-week-old male Wistar rats, ischemia/reperfusion models

1 mg/kg, 1 mL, intraperitoneally administered

–

 

Alleviating redox stress

Reduce the infarct volume and tissue swelling of ischemic hemispheres, and improve the neurological disabilities

[99]

UCNP@C60-pep

Size: 30 nm; Surface modification: Aβ-target peptide KLVFF

AD

In vivo: AD model CL2006 strain

In vitro: PC12 cells

100 µg/mL for 6 d

–

–

Alleviating redox stress and inhibiting Aβ aggregation

Prolong the lifespan of CL2006 strain

[101]

Carbogenic nanozyme

Size: ~ 2.7 nm; Surface modification: hydroxy and amide/amino groups

TBI

In vivo: 6–8-week-old male C57 BL/6 mice, TBI model

In vitro: Neuro 2A cells

5 mg/mL tail intravenously administered for 3.5 months

H2O2, ·OH, O2·−, ONOO−, ·NO

–

RONS scavenging and anti-neuroinflammation

Improve the spatial learning and memory abilities

[104]

GOQDs

Lateral sizes: 20 ~ 40 nm

PD

In vivo: larval zebrafish, MPP+-induced PD models

In vitro: PC12 cells

100 µg/mL

H2O2

–

ROS scavenging and diminishing mitochondrial damage

Reduce the expression of α-synuclein and increase locomotive activity and Nissl bodies in the brain

[106]

PEG-melanin NPs

Size: ~ 120 nm; Shape: spherical Surface modification: PEG

Ischemic stroke

In vivo: male Wistar MACO rat model

In vitro: Neuro 2A cells

10 mg/mL, stereotaxically administered

H2O2, ·OH, O2·−, ONOO−, ·NO

–

RONS scavenging and anti-neuroinflammation

Reduce the infarct volume

[5]

Hollow prussian blue NPs

Size: ~ 65 nm with an inner cavity

Ischemic stroke

In vivo: SD rats MACO models

In vitro: Raw264.7 and SH-SY5Y cells

40 μg/mL, 10 μL, stereotaxically administered

H2O2, ·OH, O2·−, ONOO−

–

ROS scavenging and anti-neuroinflammation

Alleviate the cerebral metabolic impairment, reduce the infarct volume, and attenuate the neurological deficits

[113]

  1. NPs: nanoparticles; AD: Alzheimer's disease; ROS: reactive oxygen species; PEG: polyethyleneglycol; BBB: blood–brain barrier; BCECs: brain capillary endothelial cells; MACO: middle cerebral artery occlusion; SAH: subarachnoid hemorrhage; RONS: reactive oxygen and reactive nitrogen species; ICH: intracerebral hemorrhage; Cr: chromium; TBI: traumatic brain injury; TPP: triphenylphosphonium; PD: Parkinson’s disease; MPTP: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; mitoROS: mitochondrial ROS; TH: tyrosine hydroxylase; Aβ: amyloid-β peptide; Pt: platinum; Pd: palladium; HCCs: hydrophilic carbon clusters; UCNP: upconversion NP; Pep: Aβ-target peptide KLVFF; GOQDs: graphene oxide quantum dots; MPP+: 1-methyl4-phenyl-pyridinium ion; DSPE-PEG: ethanol and polyethylene glycol phospholipid