Targeted drug delivery of nanomedicines offered a promising strategy to improve the tumor accumulation and reduce the side effects of chemotherapeutics. However, undesired recognition of the targeting ligands on the surface of nanocarriers by immune systems or normal tissues decreased the circulation time and reduced the targeting efficiency. Here, we developed a ligand-switchable micellar nanocarrier that can hide the targeting ligands when circulating in the bloodstream and expose them on the surface when entering the tumor microenvironments. With the ligand-switching capability, the nanocarrier achieved a 66% longer blood circulation half-life and a 23% higher tumor accumulation than the nanocarrier with targeting ligands on the surface. This targeting strategy could serve as a universal approach to improve the targeting efficiency for nanomedicines.
Keywords: blood circulation; immune recognition; mixed-shell micelles; switchable targeting ligands; tumor accumulation.