Self-assembled peptide-conjugated rosemary extract derivatives as drug delivery vehicles for targeting tumor cells

ABSTRACT Self-assembled supramolecular structures have gained attention due to their wide range of applications. In this work, we have created two novel drug delivery systems for targeting MCF-7 breast cancer cells using polyphenols derived from rosemary extract. The assemblies were synthesized by conjugating rosmarinic acid (RMA) and carnosic acid (CSA) with the peptide sequence H-A-I-L-L-I-T-K-G-I-F-K known for its ability to target MCF-7 breast cancer cells. The products were self-assembled into nanofibers or oblong shaped nanoassemblies. The mechanism of self-assembly was probed by COSMOS-RS computational studies. The assemblies were utilized to entrap the drug topotecan. Entrapment efficiency varied based on the morphology of the assemblies and concentration (42.3% for carnosic acid-peptide assemblies and 59.11% for rosmarinic acid-peptide assemblies). Furthermore, the RMA-peptide and CSA-peptide assemblies were found to be cytotoxic toward MCF-7 breast cancer cells, with relatively higher cytotoxicity observed for the topotecan entrapped CSA-peptide assemblies compared to topotecan entrapped RMA-peptide assemblies. Docking studies were conducted to examine binding interactions of the RMA-peptide and CSA-peptide conjugates with Src kinase receptor and estrogen receptor. Furthermore, CSA-peptide assemblies induced apoptosis while RMA-peptide assemblies induced necrosis. Our results indicate that such new biomimetic materials derived from naturally occurring polyphenols may be developed for dual targeting tumor cells.