Abstract

Triple-negative breast cancer (TNBC), an aggressive form of breast cancer, characterized by its lack of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2) poses a therapeutic challenge as common treatment options are rendered ineffective. Here is a strategy to develop a drug delivery system utilizing poly-glycinated LC129 8, a TNBC targeting peptoid, covalently attached to HK97 virus-like particles (VLP) containing a C-terminal LPETG sequence via a sortase mediated reaction. Using the properties of the cage-like structure of VLPs and the TNBC specificity of the LC129-8, high doses of chemotherapy can be efficiently loaded into the conjugate before being delivered to the affected cells inducing apoptosis. The sortase mediated conjugation to HK97 VLP was optimized and analyzed via dot blot assay with varying ratios of peptoid and sortase. Additionally, the interior of the HK97 VLP was conjugated with aldoxorubicin, a doxorubicin derivative with an acid-labile linker. The labeling of aldoxorubicin to the GP5 capsid protein was determined to be ~62%. The release study of the final construct shows the steady release of doxorubicin in an acidic buffer condition. Future analysis includes a quantitative assay determining the number of peptoid conjugated to HK97 VLP, characterization via mass spectrometry of the VLP peptoid conjugate, and in vitro selectivity/specificity analysis of the conjugate along with its ability to release its loaded cargo. This systematic method of targeted drug delivery could administer high doses of chemotherapy directly into the TNBC cells, increasing the rate of apoptosis with minimal effect to non-TNBC cells.

Date of publication

Summer 5-15-2026

Document Type

Thesis

Language

english

Persistent identifier

http://hdl.handle.net/10950/5075

Committee members

Jiyong Lee, Sean Butler, Dustin Patterson,

Degree

Master of Science in Chemistry

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