Towards in vivo photomediated delivery of anticancer peptides: Insights from pharmacokinetic and -dynamic data

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.

Komarov I.V., Tolstanova G., Kuznietsova H., Dziubenko N., Yanchuk P.I., Shtanova L.Y., Veselsky S.P., Garmanchuk L.V., Khranovska N., Gorbach O., Dovbynchuk T., Borysko P., Babii O., Schober T., Ulrich A.S., Afonin S. (2022). Towards in vivo photomediated delivery of anticancer peptides: Insights from pharmacokinetic and -dynamic data. Journal of Photochemistry and Photobiology B: Biology, 233, art. no. 112479. DOI: 10.1016/j.jphotobiol.2022.112479