Synthetic biology-instructed transdermal microneedle patch for traceable photodynamic therapy.
Humans
Photochemotherapy
/ methods
Aminolevulinic Acid
/ pharmacology
Catalase
/ metabolism
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Photosensitizing Agents
Ferrochelatase
/ metabolism
Synthetic Biology
Copper
/ metabolism
Protoporphyrins
/ metabolism
Neoplasms
/ drug therapy
Oxygen
/ metabolism
Ligases
/ metabolism
Cell Line, Tumor
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 10 2022
20 10 2022
Historique:
received:
11
04
2022
accepted:
05
10
2022
entrez:
20
10
2022
pubmed:
21
10
2022
medline:
25
10
2022
Statut:
epublish
Résumé
5-Aminolevulinic acid-based photodynamic therapy heavily depends on the biological transformation efficiency of 5-aminolevulinic acid to protoporphyrin IX, while the lack of an effective delivery system and imaging navigation are major hurdles in improving the accumulation of protoporphyrin IX and optimizing therapeutic parameters. Herein, we leverage a synthetic biology approach to construct a transdermal theranostic microneedle patch integrated with 5-aminolevulinic acid and catalase co-loaded tumor acidity-responsive copper-doped calcium phosphate nanoparticles for efficient 5-aminolevulinic acid-based photodynamic therapy by maximizing the enrichment of intratumoral protoporphyrin IX. We show that continuous oxygen generation by catalase in vivo reverses tumor hypoxia, enhances protoporphyrin IX accumulation by blocking protoporphyrin IX efflux (downregulating hypoxia-inducible factor-1α and ferrochelatase) and upregulates protoporphyrin IX biosynthesis (providing exogenous 5-aminolevulinic acid and upregulating ALA-synthetase). In vivo fluorescence/photoacoustic duplex imaging can monitor intratumoral oxygen saturation and protoporphyrin IX metabolic kinetics simultaneously. This approach thus facilitates the optimization of therapeutic parameters for different cancers to realize Ca
Identifiants
pubmed: 36266306
doi: 10.1038/s41467-022-33837-1
pii: 10.1038/s41467-022-33837-1
pmc: PMC9585024
doi:
Substances chimiques
Aminolevulinic Acid
88755TAZ87
Catalase
EC 1.11.1.6
Hypoxia-Inducible Factor 1, alpha Subunit
0
Photosensitizing Agents
0
Ferrochelatase
EC 4.99.1.1
Copper
789U1901C5
Protoporphyrins
0
Oxygen
S88TT14065
Ligases
EC 6.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6238Informations de copyright
© 2022. The Author(s).
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