Peptide nanohybrid artificial antibodies for diagnosis and therapy of breast cancer

Abstract

Antibodies are extensively used as recognition molecules for the specific binding of target molecules in sensing and therapy. However, protein antibodies are susceptible to physical perturbation and require high production cost and additional labeling for sensing. Herein, TMD (transition metal dichalcogenide)-based artificial antibodies were successfully prepared by assembling tripeptides on the TMD nanosheets for the selective recognition of human epidermal growth factor receptor 2 (HER2), leading to breast cancer diagnosis and therapy. To this end, WS2 nanosheets were obtained by liquid phase exfoliation of bulk counterparts in water and subsequently functionalized with copper-modified tripeptides (referred to as WS2-Cu-TPs). A variety of WS2-Cu-TP artificial antibody candidates were screened to find the ones that can selectively recognize HER2 using a quartz crystal microbalance (QCM). WS2-Cu-VAT was found to bind to HER2 selectively, and its binding sites were identified through epitope binning assays using anti-HER2 antibodies and molecular dynamics simulations. In addition, WS2-Cu-VAT selectively bound to HER2-overexpressing cancer cells, SK-BR-3 while its Raman signal was very weak from the HER2-negative cell MCF-7. Finally, the WS2-Cu-VAT bearing doxorubicin (DOX) selectively killed the HER2-positive cell SK-BR-3 whereas it exhibited excellent biocompatibility against normal cells. The use of such TMD artificial antibodies can be extended for diagnosis and therapy of various diseases.