Addressable Peptide Self-Assembly on the Cancer Cell Membrane for Sensitizing Chemotherapy of Renal Cell Carcinoma
© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 11 vom: 20. März, Seite e1807175 |
---|---|
1. Verfasser: | |
Weitere Verfasser: | , , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2019
|
Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
Schlagworte: | Journal Article drug delivery drug resistance peptide self-assembly supramolecular Antineoplastic Agents Peptides Doxorubicin 80168379AG |
Zusammenfassung: | © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 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 |
---|---|
Beschreibung: | Date Completed 06.06.2019 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-4095 |
DOI: | 10.1002/adma.201807175 |