LAUSR

Chemotherapy has been validated unavailable for treatment of renal cell carcinoma (RCC) in clinic due to its intrinsic drug resistance. Sensitization of chemo-drug response plays a crucial role in RCC treatment and increase of patient survival. Herein, a recognition-reaction-aggregation (RRA) cascaded strategy is utilized to in situ construct peptide-based superstructures on the renal cancer cell membrane, enabling specifically perturbing the permeability of cell membranes and enhancing chemo-drug sensitivity in vitro and in vivo. First, P1-DBCO can specifically recognize renal cancer cells by targeting carbonic anhydrase IX. Subsequently, P2-N3 is introduced and efficiently reacts with P1-DBCO to form a peptide P3, which exhibits enhanced hydrophobicity and simultaneously aggregates into a superstructure. Interestingly, the superstructure retains on the cell membrane and perturbs its integrity/permeability, allowing more doxorubicin (DOX) uptaken by renal cancer cells. Owing to this increased influx, the IC50 is significantly reduced by nearly 3.5-fold compared with that treated with free DOX. Finally, RRA strategy significantly inhibits the tumor growth of xenografted mice with a 3.2-fold enhanced inhibition rate compared with that treated with free DOX. In summary, this newly developed RRA strategy will open a new avenue for chemically engineering cell membranes with diverse biomedical applications.