|
Title
|
|
|
|
Water-soluble withaferin A polymer prodrugs via a drug-functionalized RAFT CTA approach
|
|
|
Author
|
|
|
|
|
|
|
Abstract
|
|
|
|
| To cope with the poor aqueous solubility of withaferin A, a broad-spectrum anti-cancer agent effective against therapy-resistant cancers, a polymer-drug conjugate was synthesized via a grafting-from-drug approach. Modification of withaferin A at the C27-OH with a chain transfer agent (CTA) for reversible addition-fragmentation chain transfer (RAFT) polymerization through a degradable ester bond was achieved with excellent control on the regioselectivity via a PFP-ester transesterification route. Subsequent RAFT polymerization with the hydrophilic N,N-dimethylacrylamide yielded a fully water-soluble conjugate. A decreased cytotoxicity in vitro indicated that withaferin A exists as a prodrug in the conjugate form and requires hydrolysis of the ester to regain its activity. |
|
|
|
Language
|
|
|
|
English
|
|
|
Source (journal)
|
|
|
|
European polymer journal. - Oxford
|
|
|
Publication
|
|
|
|
Oxford
:
2019
|
|
|
ISSN
|
|
|
|
0014-3057
|
|
|
DOI
|
|
|
|
10.1016/J.EURPOLYMJ.2018.11.043
|
|
|
Volume/pages
|
|
|
|
110
(2019)
, p. 313-318
|
|
|
ISI
|
|
|
|
000456751000038
|
|
|
Full text (Publisher's DOI)
|
|
|
|
|
|
|
Full text (open access)
|
|
|
|
|
|
|
Full text (publisher's version - intranet only)
|
|
|
|
|
|