Optimized Peptide Nanomaterials as Delivery Vehicles for Hydrophobic Metal-Based Anticancer Agents

<p>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.</p>

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

The Graduate School and University Center of The City University of New York

Year dc:date.available

2023

Author dc:creator

• Marciano, Yaron

Advisor dc:contributor.advisor

• Maria Contel

Committee members dc:contributor.committeemember

• Rein Ulijn
• Aneta Mieszawska
• Stephen O'Brien

• Analytical Chemistry
• Inorganic Chemistry
• Peptide self-assembly
• metal-based compounds
• cancer
• encapsulation
• N-Heterocyclic carbene
• MMP-9

Repository record dc:identifier

https://academicworks.cuny.edu/gc_etds/5151

OAI identifier oai:identifier

oai:academicworks.cuny.edu:gc_etds-6241