Self-assembled aldehyde dehydrogenase-activatable nano-prodrug for cancer stem cell-enriched tumor detection and treatment.
Neoplastic Stem Cells
/ drug effects
Animals
Humans
Aldehyde Dehydrogenase
/ metabolism
Tretinoin
/ pharmacology
Photosensitizing Agents
/ pharmacology
Mice
Cell Line, Tumor
Reactive Oxygen Species
/ metabolism
Prodrugs
/ pharmacology
Tumor Microenvironment
/ drug effects
Xenograft Model Antitumor Assays
Mice, Nude
Female
Neoplasms
/ drug therapy
Antineoplastic Agents
/ pharmacology
Mice, Inbred BALB C
Nanoparticles
/ chemistry
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:
24
04
2024
accepted:
23
10
2024
medline:
1
11
2024
pubmed:
1
11
2024
entrez:
1
11
2024
Statut:
epublish
Résumé
Cancer stem cells, characterized by high tumorigenicity and drug-resistance, are often responsible for tumor progression and metastasis. Aldehyde dehydrogenases, often overexpressed in cancer stem cells enriched tumors, present a potential target for specific anti-cancer stem cells treatment. In this study, we report a self-assembled nano-prodrug composed of aldehyde dehydrogenases activatable photosensitizer and disulfide-linked all-trans retinoic acid for diagnosis and targeted treatment of cancer stem cells enriched tumors. The disulfide-linked all-trans retinoic acid can load with photosensitizer and self-assemble into a stable nano-prodrug, which can be disassembled into all-trans retinoic acid and photosensitizer in cancer stem cells by high level of glutathione. As for the released photosensitizer, overexpressed aldehyde dehydrogenase catalyzes the oxidation of aldehydes to carboxyl under cancer stem cells enriched microenvironment, activating the generation of reactive oxygen species and fluorescence emission. This generation of reactive oxygen species leads to direct killing of cancer stem cells and is accompanied by a noticeable fluorescence enhancement for real-time monitoring of the cancer stem cells enriched microenvironment. Moreover, the released all-trans retinoic acid, as a differentiation agent, reduce the cancer stem cells stemness and improve the cancer stem cells enriched microenvironment, offering a synergistic effect for enhanced anti-cancer stem cells treatment of photosensitizer in inhibition of in vivo tumor growth and metastasis.
Identifiants
pubmed: 39482286
doi: 10.1038/s41467-024-53771-8
pii: 10.1038/s41467-024-53771-8
doi:
Substances chimiques
Aldehyde Dehydrogenase
EC 1.2.1.3
Tretinoin
5688UTC01R
Photosensitizing Agents
0
Reactive Oxygen Species
0
Prodrugs
0
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9417Subventions
Organisme : National University of Singapore (NUS)
ID : A-0009163-01-00
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32000992
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82073779
Informations de copyright
© 2024. The Author(s).
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