Dissertations, Theses, and Capstone Projects

Date of Degree

2-2023

Document Type

Dissertation

Degree Name

Ph.D.

Program

Chemistry

Advisor

Maria Contel

Committee Members

Rein Ulijn

Aneta Mieszawska

Stephen O'Brien

Subject Categories

Analytical Chemistry | Inorganic Chemistry

Keywords

Peptide self-assembly, metal-based compounds, cancer, encapsulation, N-Heterocyclic carbene, MMP-9

Abstract

Enzyme-responsive materials have been well explored, particularly as therapeutic and diagnostic agents. In this thesis we demonstrate that anionic self-assembling peptides can be utilized as delivery vehicles for metal-based hydrophobic payloads. The tunability of the system is highlighted as well as the increase in cytotoxicity and selectivity in vitro. The rapid degradation of peptides in cell media may lead to the formation of new peptide-drug bioconjugates with increased activity and selectivity. The physiological stability of these peptide delivery vehicles has been optimized by capping the N-terminus with an acetyl group. This simple backbone modification was shown to not prevent self-assembly, the ability to load hydrophobic payloads, or modify the anticancer activity in vitro. This modification decreases peptide recognition by non-specific proteases, while retaining specificity towards an enzyme of interest (MMP-9). This highlights its potential as a stable enzyme-responsive delivery system.

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