Boron Clusters Escort Doxorubicin Squashing Into Exosomes and Overcome Drug Resistance

Abstract Exosome‐based drug delivery holds significant promise for cancer chemotherapy. However, current methods for loading drugs into exosomes are inefficient and cost‐prohibitive for practical application. In this study, boron clusters are mixed with doxorubicin (DOX) and exosomes, enabling the efficient encapsulation of DOX into exosomes through a superchaotropic effect. Exosomes loaded with DOX and boron clusters (EDB) exhibit superior permeability and the ability to deliver higher concentrations of DOX into DOX‐resistant breast cancer cells. Mechanistic analysis reveals that boron clusters form a supramolecular complex with DOX, which facilitates sustained drug release and effectively inhibits P‐glycoprotein‐mediated DOX efflux. As a result, EDB significantly enhance apoptosis in DOX‐resistant breast cancer cells and suppress tumor growth in cases where DOX alone is ineffective, thereby extending the survival of nude mice. In summary, boron clusters effectively facilitate the incorporation of DOX into exosomes and inhibit DOX efflux, offering a novel strategy to overcome DOX resistance.