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

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...

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Bibliographic Details
Published in:Pharmaceutics 2020-06, Vol.12 (6), p.576
Main Authors: Dókus, Levente E., Lajkó, Eszter, Ranđelović, Ivan, Mező, Diána, Schlosser, Gitta, Kőhidai, László, Tóvári, József, Mező, Gábor
Format: Article
Language:English
Subjects:
Amino acids
antitumor peptide conjugates
Cancer therapies
Chemotherapy
daunomycin
homing peptide
Medical prognosis
Medical research
Mortality
Nanoparticles
oxime linkage
Pancreatic cancer
Peptides
Pore size
targeted tumor therapy
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Summary: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.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics12060576