Tumor-targeted glutathione oxidation catalysis with ruthenium nanoreactors against hypoxic osteosarcoma.
Osteosarcoma
/ drug therapy
Animals
Glutathione
/ metabolism
Oxidation-Reduction
Mice
Humans
Cell Line, Tumor
Catalysis
Ruthenium
/ chemistry
Reactive Oxygen Species
/ metabolism
Bone Neoplasms
/ drug therapy
Antineoplastic Agents
/ pharmacology
TRPM Cation Channels
/ metabolism
Female
Xenograft Model Antitumor Assays
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
31 Oct 2024
31 Oct 2024
Historique:
received:
28
09
2023
accepted:
16
10
2024
medline:
31
10
2024
pubmed:
31
10
2024
entrez:
31
10
2024
Statut:
epublish
Résumé
The majority of anticancer agents have a reduced or even complete loss of a therapeutic effect within hypoxic tumors. To overcome this limitation, research efforts have been devoted to the development of therapeutic agents with biological mechanisms of action that are independent of the oxygen concentration. Here we show the design, synthesis, and biological evaluation of the incorporation of a ruthenium (Ru) catalyst into polymeric nanoreactors for hypoxic anticancer therapy. The nanoreactors can catalyze the oxidation of glutathione (GSH) to glutathione disulfide (GSSG) in hypoxic cancer cells. This initiates the buildup of reactive oxygen species (ROS) and lipid peroxides, leading to the demise of cancer cells. It also stimulates the overexpression of the transient receptor potential melastatin 2 (TRPM2) ion channels, triggering macrophage activation, leading to a systemic immune response. Upon intravenous injection, the nanoreactors can systemically activate the immune system, and nearly fully eradicate an aggressive osteosarcoma tumor inside a mouse model.
Identifiants
pubmed: 39477929
doi: 10.1038/s41467-024-53646-y
pii: 10.1038/s41467-024-53646-y
doi:
Substances chimiques
Glutathione
GAN16C9B8O
Ruthenium
7UI0TKC3U5
Reactive Oxygen Species
0
Antineoplastic Agents
0
TRPM Cation Channels
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9405Subventions
Organisme : Natural Science Foundation of Beijing Municipality (Beijing Natural Science Foundation)
ID : JQ24055
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 22175189; 52373127
Informations de copyright
© 2024. The Author(s).
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