Virion-Like Membrane-Breaking Nanoparticles with Tumor-Activated Cell-and-Tissue Dual-Penetration Conquer Impermeable Cancer
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 27 vom: 17. Juli, Seite e1707240 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2018
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| Zugriff auf das übergeordnete Werk: | Advanced materials (Deerfield Beach, Fla.) |
| Schlagworte: | Journal Article impermeable cancer membrane-breaking capacity multidrug resistance reversal tumor penetration virion-like nanoparticles Peptides |
| Zusammenfassung: | © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Poor drug penetration into tumor cells and tissues is a worldwide difficulty in cancer therapy. A strategy is developed for virion-like membrane-breaking nanoparticles (MBNs) to smoothly accomplish tumor-activated cell-and-tissue dual-penetration for surmounting impermeable drug-resistant cancer. Tailor-made dendritic arginine-rich peptide prodrugs are designed to mimic viral protein transduction domains and globular protein architectures. Attractively, these protein mimics self-assemble into virion-like nanoparticles in aqueous solution, having highly ordered secondary structure. Tumor-specific acidity conditions would activate the membrane-breaking ability of these virion-like nanoparticles to perforate artificial and natural membrane systems. As expected, MBNs achieve highly efficient drug penetration into drug-resistant human ovarian (SKOV3/R) cancer cells. Most importantly, the well-organized MBNs can pass through endothelial/tumor cells and spread from one cell to another one. Intravenous injection of MBNs into nude mice bearing impermeable SKOV3/R tumors suggests that the MBNs can recognize the tumor tissue after prolonged blood circulation, evoke the membrane-breaking function for robust transvascular extravasation, and penetrate into the deep tumor tissue. This work provides the first demonstration of sophisticated molecular and supramolecular engineering of virion-like MBNs to realize the long-awaited cell-and-tissue dual-penetration, contributing to the development of a brand-new avenue for dealing with incurable cancers |
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| Beschreibung: | Date Completed 06.03.2019 Date Revised 30.09.2020 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.201707240 |