Development of new amphiphilic bio-organic assemblies for potential applications in iron-binding and targeting tumor cells

ABSTRACT

Iron overload has been implicated in the pathogenesis of many neurodegenerative diseases, cancer and thalassemia. In this work, we have developed new supramolecular assemblies as potential iron chelators for mitigating iron overload at the cellular level. We utilized fluorenyl-based building blocks that were functionalized with ethylene diamine (Fmoc-Ed) or arginine (Fmoc-Arg). Fmoc-Ed was further conjugated with ureido propionic acid (UDP) or pyrazole-3-carboxylic acid (PCA). Each of the building blocks were self-assembled into nanovesicles or fibers and further functionalized with the transferrin receptor binding peptide THRPPMWSPVWP (Tf) to promote receptor mediated cellular uptake. Our results indicated that the assemblies were able to target HeLa cells, induce apoptosis, ROS formation and were able to penetrate the cells. The degree of cellular impact was dependent upon the structure of the assemblies. The effects were more prominent under iron overload conditions compared to normal growth conditions. Our results suggest that such nanoscale assemblies may open new avenues for further studies into iron chelation and mitigation of iron overload using Fmoc-functionalized building blocks.

Keywords:

• Nanoassemblies
• iron chelation
• self-assembly
• cell-targeting

Acknowledgments

The authors thank Fordham University Research Grants for financial support of this work. M. H. thanks Harrison Pajovich for acquisition of the NMR data. The authors would also like to thank Dr. Karl Fath at the Queens College core facility for Imaging, Cellular, and Molecular Biology for the use of the transmission electron microscope.

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Additional information

Funding

This work was indeed supported by the Fordham University Research Grants.