Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo.
Animals
Bacterial Infections
/ drug therapy
Coculture Techniques
Fluorescent Dyes
/ administration & dosage
Glioblastoma
/ drug therapy
Humans
Intravital Microscopy
Light
Microbial Sensitivity Tests
Microscopy, Confocal
Microscopy, Fluorescence
Organoselenium Compounds
/ administration & dosage
Photochemotherapy
/ methods
Spheroids, Cellular
Xenograft Model Antitumor Assays
Zebrafish
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
22 04 2021
22 04 2021
Historique:
received:
24
10
2020
accepted:
19
03
2021
entrez:
23
4
2021
pubmed:
24
4
2021
medline:
12
5
2021
Statut:
epublish
Résumé
Photoactivatable molecules enable ablation of malignant cells under the control of light, yet current agents can be ineffective at early stages of disease when target cells are similar to healthy surrounding tissues. In this work, we describe a chemical platform based on amino-substituted benzoselenadiazoles to build photoactivatable probes that mimic native metabolites as indicators of disease onset and progression. Through a series of synthetic derivatives, we have identified the key chemical groups in the benzoselenadiazole scaffold responsible for its photodynamic activity, and subsequently designed photosensitive metabolic warheads to target cells associated with various diseases, including bacterial infections and cancer. We demonstrate that versatile benzoselenadiazole metabolites can selectively kill pathogenic cells - but not healthy cells - with high precision after exposure to non-toxic visible light, reducing any potential side effects in vivo. This chemical platform provides powerful tools to exploit cellular metabolic signatures for safer therapeutic and surgical approaches.
Identifiants
pubmed: 33888691
doi: 10.1038/s41467-021-22578-2
pii: 10.1038/s41467-021-22578-2
pmc: PMC8062536
doi:
Substances chimiques
Fluorescent Dyes
0
Organoselenium Compounds
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2369Subventions
Organisme : Wellcome Trust
ID : 100104/Z/12/Z
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C38363/A26931
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N013166/1
Pays : United Kingdom
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