Phage Display-Based Homing Peptide-Daunomycin Conjugates for Selective Drug Targeting to PANC-1 Pancreatic Cancer.

Autor: Dókus LE; MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, 1117 Budapest, Hungary.; Institute of Chemistry, Faculty of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary., Lajkó E; Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, Hungary., Ranđelović I; National Institute of Oncology, Department of Experimental Pharmacology, 1122 Budapest, Hungary., Mező D; Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, Hungary., Schlosser G; MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, 1117 Budapest, Hungary.; Institute of Chemistry, Faculty of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary., Kőhidai L; Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Budapest, Hungary., Tóvári J; National Institute of Oncology, Department of Experimental Pharmacology, 1122 Budapest, Hungary., Mező G; MTA-ELTE Research Group of Peptide Chemistry, Hungarian Academy of Sciences, 1117 Budapest, Hungary.; Institute of Chemistry, Faculty of Sciences, Eötvös Loránd University, 1117 Budapest, Hungary.
Jazyk: angličtina
Zdroj: Pharmaceutics [Pharmaceutics] 2020 Jun 22; Vol. 12 (6). Date of Electronic Publication: 2020 Jun 22.
DOI: 10.3390/pharmaceutics12060576
Abstrakt: The Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most aggressive and dangerous cancerous diseases, leading to a high rate of mortality. Therefore, the development of new, more efficient treatment approaches is necessary to cure this illness. Peptide-based drug targeting provides a new tool for this purpose. Previously, a hexapeptide Cys-Lys-Ala-Ala-Lys-Asn (CKAAKN) was applied efficiently as the homing device for drug-loaded nanostructures in PDAC cells. In this research, Cys was replaced by Ser in the sequence and this new SKAAKN targeting moiety was used in conjugates containing daunomycin (Dau). Five different structures were developed and tested. The results indicated that linear versions with one Dau were not effective on PANC-1 cells in vitro; however, branched conjugates with two Dau molecules showed significant antitumor activity. Differences in the antitumor effect of the conjugates could be explained with the different cellular uptake and lysosomal degradation. The most efficient conjugate was Dau=Aoa -GFLG-K( Dau=Aoa )SKAAKN- OH (conjugate 4 ) that also showed significant tumor growth inhibition on s.c. implanted PANC-1 tumor-bearing mice with negligible side effects. Our novel results suggest that peptide-based drug delivery systems could be a promising tool for the treatment of pancreatic cancers.
Databáze: MEDLINE
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