Investigating the Potential Cytotoxic Effects of an NGR-Tagged Ruthenium Rubredoxin on HT1080 Fibrosarcoma Cells

Date of Award

6-2024

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Francis E. Jenney, Jr.

Second Advisor

Kimberly Baker

Third Advisor

Lori Redmond

Abstract

Many forms of cancer, such as fibrosarcoma, present significant challenges in treatment due to their aggressive nature, individual presentation, and limited therapeutic options. In recent research, the development of anticancer agents targeting specific biomarkers such as aminopeptidase N (CD13), overexpressed by cancer cells like fibrosarcoma, may enhance treatment efficacy while minimizing collateral adverse effects. A promising approach involves the utilization of NGR-tagged compounds, which have demonstrated a “trojan horse” property in preclinical studies. Ruthenium-based compounds have also garnered attention as a potential alternative to platinumbased antineoplastic agents in treating a variety of malignancies.

This research aimed to investigate the cytotoxic effects of an NGR-tagged ruthenium-substituted rubredoxin (NGR-RuRb) compound on fibrosarcoma cells. Through a series of in vitro assays, including cell viability assays, apoptosis assays, and cellular uptake imaging, the impact of NGR-RuRb on cell lines possessing an NGR receptor, aminopeptidase N, was evaluated.

Preliminary results demonstrate a greater dose-dependent decrease in fibrosarcoma cell viability following treatment when compared to an aminopeptidase N null cell line. The resulting images from fluorescence microscopy revealed more NGR-RuRb around HT1080 cells, suggesting efficient targeted delivery to cancer cells expressing NGR-binding receptors.

These findings underscore the potential of NGR-tagged rutheniumsubstituted rubredoxin compounds as a novel therapeutic strategy for fibrosarcoma treatment and its potential as an antineoplastic agent for other aminopeptidase N-expressing cancer lines. Further studies are warranted to optimize compound efficacy, elucidate mechanistic effects, and evaluate its therapeutic potential in in vivo models. Ultimately, and optimistically, the effects of NGR-RuRb may translate into clinical applications for combating fibrosarcoma and other aminopeptidase N targetable malignancies.

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