Target-Specific TMD Nanosheet Antagonists for Treatment of Breast Cancer

Abstract

Antibodies are widely employed as selective recognition molecules that can bind to specific target antigens in sensing and therapy. However, the conventional development and production of antibodies require time-consuming and complex high-cost procedures. In addition, their therapeutic efficacy is often limited in clinical applications. In this study, we designed a target protein-selective transition metal dichalcogenide (TMD) nanosheet antagonist that exhibits strong binding affinity and intense Raman scattering signals for the treatment of breast cancer. To impart high recognition selectivity toward HER2 overexpressed on breast cancer cells to the TMD nanosheet antagonist, various types of tripeptide assemblies (TPAs) were created on the TMD surface as flexible recognition motifs. The selected TMD-TPA exhibited a strong HER2-binding affinity of approximately 0.84 nM, and the epitope binning assay and molecular dynamics simulations were performed to precisely identify the binding regions of HER2 recognized by the corresponding antagonist. Moreover, the TMD-TPA could selectively bind to HER2-positive cells, in which its strong Raman signals were observed, whereas HER2-negative cells showed the negligible signals of the TMD-TPA. The developed TMD-TPA antagonist effectively suppressed tumor growth in vitro and in vivo, thereby enhancing the therapeutic efficacy in mice models.