Selectively Potentiating Hypoxia Levels by Combretastatin A4 Nanomedicine Toward Highly Enhanced Hypoxia-Activated Prodrug Tirapazamine Therapy for Metastatic Tumors

Selectively Potentiating Hypoxia Levels by Combretastatin A4 Nanomedicine : Toward Highly Enhanced Hypoxia-Activated Prodrug Tirapazamine Therapy for Metastatic Tumors

© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 31(2019), 11 vom: 05. März, Seite e1805955
1. Verfasser: Yang, Shengcai (VerfasserIn)
Weitere Verfasser: Tang, Zhaohui, Hu, Chenyang, Zhang, Dawei, Shen, Na, Yu, Haiyang, Chen, Xuesi
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article hypoxia hypoxia-activated prodrug metastatic breast carcinoma nanomedicine vascular disrupting agent Prodrugs Stilbenes Tirapazamine 1UD32YR59G mehr... fosbretabulin I5590ES2QZ
Beschreibung
Zusammenfassung:© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Hypoxia-activated prodrugs (HAPs) have the potential to selectively kill hypoxic cells and convert tumor hypoxia from a problem to a selective treatment advantage. However, HAPs are unsuccessful in most clinical trials owing to inadequate hypoxia within the treated tumors, as implied by a further substudy of a phase II clinical trial. Here, a novel strategy for the combination of HAPs plus vascular disrupting agent (VDA) nanomedicine for efficacious solid tumor therapy is developed. An effective VDA nanomedicine of poly(l-glutamic acid)-graft-methoxy poly(ethylene glycol)/combretastatin A4 (CA4-NPs) is prepared and can selectively enhance tumor hypoxia and boost a typical HAP tirapazamine (TPZ) therapy against metastatic 4T1 breast tumors. After treatment with the combination of TPZ plus CA4-NPs, complete tumor reduction is observed in 4T1 xenograft mice (initial tumor volume is 180 mm3 ), and significant tumor shrinkage and antimetastatic effects are observed in challenging large tumors with initial volume of 500 mm3 . The report here highlights the potential of using a combination of HAPs plus VDA nanomedicine in solid tumor therapy
Beschreibung:Date Completed 06.06.2019
Date Revised 30.09.2020
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-4095
DOI:10.1002/adma.201805955