Targeted Thyroid Cancer Therapy Using Peptide-Loaded Hydrogels

Abstract

Thyroid cancer is the most prevalent endocrine malignancy globally, with papillary thyroid carcinoma being the dominant subtype and exhibiting a rising incidence. Mutations in the BRAF gene are responsible for the majority of thyroid cancers. The BRAF gene encodes the BRAF protein, which plays a role in the MAPK/ERK signaling pathway that regulates cell growth and division. The BRAF mutation causes continuous activation of the BRAF protein, resulting in constant MEK and ERK activation. This leads to uncontrolled cell division and tumor formation. Conventional treatments such as thyroidectomy and radioiodine ablation lack tumor specificity and often harm healthy tissues. Therefore, there is a need for therapeutic strategies that can slow down tumor development and selectively kill cancer cells without damaging healthy tissues. DR8 peptide is an antifibrotic agent that functions by inhibiting the MAPK/ERK pathway involved in fibrosis formation. Considering the mechanism of tumor formation in papillary thyroid carcinoma, it is hypothesized that the DR8 peptide may also inhibit cancerous cell growth and induce cell death. In this study, a functional self-assembling peptide (SAP) hydrogel including DR8 peptide is designed for the treatment of papillary thyroid carcinoma. The effectiveness of the developed hydrogel system was evaluated on BCPAP and L929 cell lines. Cells were incubated with the soluble form of the DR8 peptide at various concentrations. While the DR8 peptide induced 40–50% cancer cell death with 40 μM DR8, it exhibited no cytotoxicity on healthy cells. Since the effectiveness of the DR8 peptide was proven on the BCPAP cell line, an injectable SAP hydrogel system consisting of KLDL SAP and the DR8 peptide was developed by synthesizing KLDL and DR8 end-to-end with Gly-Gly-Gly linkers. Future studies will b conductd to explore the effect of KLDL/DR8 hydrogels on BCPAP and L929 cell lines.