2024 AIChE Annual Meeting

Egfr Binding Peptide Contrast Agents for Signaling Egfr-Positive Tumors

Triple Negative Breast Cancer, TNBC, is an aggressive and fast-growing subtype of Breast
Cancer, which lacks an established therapeutic target. It is characterized by the absence of
increased expression of the estrogen receptor, progesterone receptor, and human epidermal
growth factor receptor 2 (HER2). Additionally, TNBC affects 13 in every 100,000 women in the
United States. Magnetic Resonance Imaging, MRI, is the main noninvasive method to detect
these tumors. However, due to TNBC’s unique characteristics and nonuniform shape, it is more
likely to have inaccuracies in the diagnosis of the tumor and/or tumor morphology. A
gadolinium-based contrast agent chelated by an Epidermal Growth Factor Receptor (EGFr)
binding peptide is being developed to address these limitations in MRIs. The use of this
conjugate will improve the contrast in MRI scans, leading to more accurate detections of
EGFr-positive tumors, such as the most common subtypes of TNBC. The conjugate will bind to
EGFr, where the paramagnetic gadolinium ions will interact with water molecules in tissues,
influencing relaxation rates on MRI scans. EGFr-binding peptides were synthesized by
Solid-Phase Peptide Synthesis and coupled with a chelating agent. The main peptide, AEGFr,
was found in previous literature and was linked to self-assembling peptides previously developed
in KumarLab to develop novel self-assembling multidomain peptides SAP1-AEGFr and
SAP2-AEGFr. The peptide conjugates were synthesized and characterized for their chemical,
structural, and mechanical properties. The affinity of self-assembling conjugated peptides to the
EGFr needs to be further tested with Microscale Thermophoresis, MST to find the best binding
affinity. Next, the peptide conjugates are combined with a gadolinium(III) ion solution. The
peptide will then self-aggregate to form a translucent soft hydrogel. The formed EGFr Binding
Peptide Contrast Agent can then be injected into a patient, increasing the accuracy of EGFr+
tumor diagnosis.

Figure 1: Schematic of Experimental Procedure. Created with BioRender.com