Concurrent Drug Unplugging and Permeabilization of Polyprodrug-Gated Crosslinked Vesicles for Cancer Combination Chemotherapy
© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
| Veröffentlicht in: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 21 vom: 11. Mai, Seite e1706307 |
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| 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 combination chemotherapy gated crosslinked vesicles permeabilization polyprodrug amphiphiles therapeutic activation Polymers Doxorubicin 80168379AG Camptothecin |
| Zusammenfassung: | © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Combination chemotherapy with both hydrophobic and hydrophilic therapeutic drugs is clinically vital toward the treatment of persistent cancers. Though conventional liposomes and polymeric vesicles possessing hydrophobic bilayers and aqueous interiors can serve as codelivery nanocarriers, it remains a considerable challenge to achieve synchronized release of both types of drugs due to distinct encapsulation mechanisms; premature release of water-soluble cargos from unstable liposomes and ruptured vesicles is also a major concern. Herein, the fabrication of physiologically stable polyprodrug-gated crosslinked vesicles (GCVs) via the self-assembly of camptothecin (CPT) polyprodrug amphiphiles and in situ bilayer crosslinking through traceless sol-gel reaction is reported. Polyprodrug-GCVs possess high CPT loading (>30 wt%) and minimized leakage of encapsulated hydrophilic doxorubicin (DOX) hydrochloride due to the suppressed permeability of crosslinked membrane, exhibiting extended blood circulation (t 1/2 > 13 h) with caged cytotoxicity in physiological circulation. Upon cellular uptake by cancer cells, cytosolic reductive milieu-triggered CPT unplugging from vesicle bilayers is demonstrated to generate hydrophilic mesh channels and make the membrane highly permeable. Concurrently, it will promote DOX corelease from hydrophilic lumen (≈36-fold increase). The reduction-activated combination chemotherapeutic potency based on polyprodrug-GCVs is confirmed by both in vitro and in vivo explorations |
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| Beschreibung: | Date Completed 07.03.2019 Date Revised 30.09.2020 published: Print-Electronic ErratumIn: Adv Mater. 2019 Oct;31(43):e1903849. - PMID 31639275 Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.201706307 |