https://orcid.org/0000-0002-6987-9717
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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.
Acknowledgments
The authors thank Fordham University Research Grants for financial support of this work.
Conflict of Interest
The authors declare no conflict of interest.