Thesis Format

Integrated Article

Synthesis and modification of cyclic peptide nanotubes as imaging agents

Author

FATIMA AMANDA SANTILLAN ESPINOZA, The University of Western OntarioFollow

Degree

Master of Science

Program

Chemistry

Collaborative Specialization

Molecular Imaging

Supervisor

Luyt, Leonard G.

Abstract

Peptide-based nanoassemblies have emerged as a promising avenue in chemistry, nanotechnology, and cancer diagnosis, opening new opportunities for advancement. This thesis describes the development of imaging nanoprobes based on the co-assembly of a series D,L-α cyclic octapeptides in an aqueous environment. This innovative strategy involves the incorporation of four distinct cyclic peptides, each with specific features crucial for the design of the imaging probe. Nanotubes were generated by co-assembly of an unmodified peptide, a PEGylated peptide, a fluorescein-labeled peptide, and a PSMA-targeting cyclic peptide within a single solution. These resulting co-assembled nanotubes exhibit potential for optical imaging in the context of prostate cancer.

Summary for Lay Audience

Peptides are small portions of proteins that generally are linear and widely applied in molecular imaging. However, they display poor in vivo stability and reduced specific binding to molecular targets. When peptides are cyclized, free carboxy and amino ends are lacking, forming ring-like structures, and rendering more chemically stable versions. This circular arrangement gives cyclic peptides unique properties, often increasing the resistance to enzymatic degradation and improving their targeting abilities. These distinct features make cyclic peptides better candidates than their linear counterparts for biomedical applications.

Several studies have shown the ability of cyclic peptides with eight D- and L- amino acids to form nanotubes through self-assembly. Since the surface of cyclic peptides can be modified through their side chains, attaching polymers, fluorophores or ligands confer new functional properties to the surface of the nanotubes. This thesis discusses the incorporation of different molecules to the surface of the cyclic peptides to develop a system with desired functional properties for optical imaging of prostate cancer.

This research focuses on the cyclization of linear octapeptides derived from the sequence cyclo-(D-L-K-D-L-Y)₂. The modifications and final peptide products were characterized and purified using reverse-phase high-performance liquid chromatography. A ligand based on prostate-specific membrane antigen was incorporated to target prostate cancer cells. Subsequently, the self-assembly of the purified cyclic materials was studied and the resulting nanostructures were evaluated by electron microscopy techniques and spectroscopic methods. Thus, the co-assembly of the cyclic peptides is also described and performed to generate a molecular imaging probe with potential targeting for prostate cancer. This approach provides new insight into applying of self-assembled cyclic peptide nanotubes in molecular imaging.

Recommended Citation

SANTILLAN ESPINOZA, FATIMA AMANDA, "Synthesis and modification of cyclic peptide nanotubes as imaging agents" (2023). Electronic Thesis and Dissertation Repository. 9471.
https://ir.lib.uwo.ca/etd/9471

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