Towards in vivo photomediated delivery of anticancer peptides: Insights from pharmacokinetic and -dynamic data.
J Photochem Photobiol B
; 233: 112479, 2022 Aug.
Article
em En
| MEDLINE
| ID: mdl-35660309
ABSTRACT
An in vivo study of a photoswitchable cytotoxic peptide LMB040 has been undertaken on a chemically induced hepatocellular carcinoma model in immunocompetent rats. We analysed the pharmacokinetic profile of the less toxic photoform ("ring-closed" dithienylethene) of the compound in tumors, plasma, and healthy liver. Accordingly, the peptide can reach a tumor concentration sufficiently high to exert a cytotoxic effect upon photoconversion into the more active ("ring-open") photoform. Tissue morphology, histology, redox state of the liver, and hepatic biochemical parameters in blood serum were analysed upon treatment with (i) the less active photoform, (ii) the in vivo light-activated alternative photoform, and (iii) compared with a reference chemotherapeutic 5-fluorouracil. We found that application of the less toxic form followed by a delayed in vivo photoconversion into the more toxic ring-open form of LMB040 led to a higher overall survival of the animals, and signs of enhanced immune response were observed compared to the untreated animals.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
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Antineoplásicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article