Antioxidant and C5a-blocking strategy for hepatic ischemia-reperfusion injury repair.
Animals
Antioxidants
/ metabolism
Cerium
Complement C5a
/ metabolism
Cytokines
/ metabolism
Disease Models, Animal
Female
Inflammation
Inflammation Mediators
/ metabolism
Ischemia
Liver
/ metabolism
Mice
Nanomedicine
Oxidative Stress
/ drug effects
RAW 264.7 Cells
Reactive Oxygen Species
/ metabolism
Reperfusion Injury
/ drug therapy
Aptamer
C5a
Hepatic ischemia–reperfusion injury
Nanoantioxidants
Nanoceria
Journal
Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208
Informations de publication
Date de publication:
15 Apr 2021
15 Apr 2021
Historique:
received:
21
02
2021
accepted:
08
04
2021
entrez:
16
4
2021
pubmed:
17
4
2021
medline:
15
10
2021
Statut:
epublish
Résumé
Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials' propensity for liver distribution might enable their use in hepatic ischemia-reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair. To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited. The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases.
Sections du résumé
BACKGROUND
BACKGROUND
Nonspecific liver uptake of nanomaterials after intravenous injection has hindered nanomedicine for clinical translation. However, nanomaterials' propensity for liver distribution might enable their use in hepatic ischemia-reperfusion injury (IRI) repair. During hepatic IRI, reactive oxygen species (ROS) are generated and the fifth component of complement (C5a) is activated. In addition, C5a is confirmed to exacerbate the vicious cycle of oxidative stress and inflammatory damage. For these reasons, we have investigated the development of nanomaterials with liver uptake to scavenge ROS and block C5a for hepatic IRI repair.
RESULTS
RESULTS
To achieve this goal, a traditional nanoantioxidant of nanoceria was surface conjugated with the anti-C5a aptamers (Ceria@Apt) to scavenge the ROS and reduce C5a-mediated inflammation. High uptake of Ceria@Apt in the liver was confirmed by preclinical positron emission tomography (PET) imaging. The clinical symptoms of hepatic IRI were effectively alleviated by Ceria@Apt with ROS scavenging and C5a blocking in mice model. The released pro-inflammatory cytokines were significantly reduced, and subsequent inflammatory reaction involved in the liver was inhibited.
CONCLUSIONS
CONCLUSIONS
The synthesized Ceria@Apt has great potential of medical application in hepatic IRI repair, which could also be applied for other ischemic-related diseases.
Identifiants
pubmed: 33858424
doi: 10.1186/s12951-021-00858-9
pii: 10.1186/s12951-021-00858-9
pmc: PMC8050892
doi:
Substances chimiques
Antioxidants
0
Cytokines
0
Inflammation Mediators
0
Reactive Oxygen Species
0
Cerium
30K4522N6T
ceric oxide
619G5K328Y
Complement C5a
80295-54-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Subventions
Organisme : the National Institutes of Health
ID : P30CA014520
Organisme : Multidisciplinary Cross-Project (Medical) of Shanghai Jiao Tong University
ID : YG2017MS65
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