Harnessing engineered protein versatility for theranostics

Liver fibrosis and tumour progression are partly driven by TGF-β signalling, which depends on the molecular chaperone Hsp90. To address the limitations of conventional Hsp90 inhibitors, the engineered protein C390 was designed to selectively disrupt the TGF-β–Hsp90 interaction while preserving the essential chaperone activity of Hsp90.

Ana Beloqui Garcia (WEL Research Institute – UCLouvain) and colleagues further modified C390 by adding a gold-binding module, thereby integrating therapeutic and imaging functions within a single construct without compromising C390 stability. The resulting nanohybrid, C390-AuNC, reduced fibrosis, promoted collagen degradation, and lowered tumour burden in mouse models of liver fibrosis and hepatocellular carcinoma. These results highlight the versatility of engineered proteins, which can be functionalized with metal-binding domains (e.g., gold or gadolinium) to enable theranostic applications combining therapy and imaging.

Saxena et al, Engineered protein nanoclusters reduce liver fibrosis and hepatocellular carcinoma in mice models, Bioact Mater (2026) 65: 14-27