Targeted α3β1 Integrin-Specific HSPC Peptide Modified Liposomes Designed to Target Metastatic Breast Cancer
Abstract: The utilization of liposomes as drug delivery systems can serve as an effective method in the treatment of a variety of cancers due to their ability to improve therapeutic and pharmacological properties of chemotherapeutics. One possible disadvantage in current therapies is the lack of targeting capabilities to selectively bind cancerous versus non-cancerous cells. However, liposomes are readily modifiable to include targeting ligands such as peptides, which have the potential to preferentially bind upregulated cell surface receptors on cancer cells. One such receptor, the α3β1 integrin, is known to be overexpressed in metastatic breast cancer. In this study, we have incorporated a unique peptide construct directly into the liposomal bilayer, which is known to bind this particular receptor. We first verified the presence of the peptide within the liposomal bilayer using absorbance spectroscopy. Subsequent stability studies were then conducted on liposomes both with and without the targeting peptide to determine if its presence influenced the overall structural integrity of the liposome. No significant difference in stability was observed in either system, suggesting a stable system with potential targeting capabilities. We then tested the selectivity of the liposomes by measuring fluorophore accumulation in both metastatic breast cancer cells (MDA-MB-231) as well as non-cancerous cells (MCF-10A), following whole cell ELISA experiments used to verify the upregulation of the α3β1 integrin in the MDA-MB-231 cells compared to MCF-10A cells.
Shelby M. Phelps*, Alexandra E. Muniz, Dr. Jason C. Yarbrough, and Dr. David R. Khan
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