Cell-Selective Delivery of RIBOTACs via an Anti-EGFR Nanobody for Pancreatic Cancer Treatment

This study develops a dual-targeting, bioresponsive nanobody-RIBOTAC for pancreatic ductal adenocarcinoma. An EGFR-targeting nanobody-Fc fusion and a cathepsin B-responsive linker deliver a miR-21-specific RIBOTAC into tumors, addressing limitations in tissue penetration and tumor selectivity. In orthotopic pancreatic cancer models, the construct achieved 60% miR-21 knockdown while sparing normal tissues and significantly inhibited tumor growth, supporting a modular strategy for precision RNA degradation in difficult-to-treat cancers.