Concurrent Drug Unplugging and Permeabilization of Polyprodrug-Gated Crosslinked Vesicles for Cancer Combination Chemotherapy

© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 30(2018), 21 vom: 11. Mai, Seite e1706307
1. Verfasser: Hu, Xianglong (VerfasserIn)
Weitere Verfasser: Zhai, Shaodong, Liu, Guhuan, Xing, Da, Liang, Haojun, Liu, Shiyong
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
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 XT3Z54Z28A
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500 |a Date Revised 30.09.2020 
500 |a published: Print-Electronic 
500 |a ErratumIn: Adv Mater. 2019 Oct;31(43):e1903849. - PMID 31639275 
500 |a Citation Status MEDLINE 
520 |a © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. 
520 |a 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 
650 4 |a Journal Article 
650 4 |a combination chemotherapy 
650 4 |a gated crosslinked vesicles 
650 4 |a permeabilization 
650 4 |a polyprodrug amphiphiles 
650 4 |a therapeutic activation 
650 7 |a Polymers  |2 NLM 
650 7 |a Doxorubicin  |2 NLM 
650 7 |a 80168379AG  |2 NLM 
650 7 |a Camptothecin  |2 NLM 
650 7 |a XT3Z54Z28A  |2 NLM 
700 1 |a Zhai, Shaodong  |e verfasserin  |4 aut 
700 1 |a Liu, Guhuan  |e verfasserin  |4 aut 
700 1 |a Xing, Da  |e verfasserin  |4 aut 
700 1 |a Liang, Haojun  |e verfasserin  |4 aut 
700 1 |a Liu, Shiyong  |e verfasserin  |4 aut 
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773 1 8 |g volume:30  |g year:2018  |g number:21  |g day:11  |g month:05  |g pages:e1706307 
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