| The effect of the acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression. | |
| | |
MedLine Citation:
|
PMID: 23261218 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Chemoresistance is a major issue for most gemcitabine-related chemotherapies. The overexpression of ribonucleotide reductase subunit M1 (RRM1) plays a key role in gemcitabine resistance. In this study, we synthesized a new highly acid-sensitive amphiphilic micelle material by conjugating hydrophilic polyethylene glycol with a hydrophobic stearic acid derivative (C18) using a hydrazone bond, which was named as PHC-2. A lipophilic prodrug of gemcitabine, 4-(N)-stearoyl gemcitabine (GemC18), was loaded into micelles prepared with PHC-2, a previously synthesized less acid-sensitive PHC-1, and their acid-insensitive counterpart, PAC. GemC18 loaded in acid-sensitive micelles can overcome gemcitabine resistance, and GemC18 in the highly acid-sensitive PHC-2 micelles was more cytotoxic than in the less acid-sensitive PHC-1 micelles. Mechanistic studies revealed that upon cellular uptake and lysosomal delivery, GemC18 in the acid-sensitive micelles was released and hydrolyzed more efficiently. Furthermore, GemC18 loaded in the highly acid-sensitive PHC-2 micelles inhibited the expression of RRM1 and increased the level of gemcitabine triphosphate (dFdCTP) in gemcitabine resistant tumor cells. The strategy of delivering lipophilized nucleoside analogs using highly acid-sensitive micelles may represent a new platform technology to increase the antitumor activity of nucleoside analogs and to overcome tumor cell resistance to them. |
| | |
Authors:
|
Saijie Zhu; Piyanuch Wonganan; Dharmika S P Lansakara-P; Hannah L O'Mary; Yue Li; Zhengrong Cui |
Related Documents
:
|
23453798 - Preparation and characterization of biomass carbon-based solid acid catalyst for the es... 9619588 - Isolation and characterization of two forms of an acidic bromelain stem proteinase. 6783658 - Amino acid sequence of a myoglobin isolated from map turtle, graptemys geographica. 16734778 - Functional effects of amino acid substitutions within the large binding pocket of the p... 7954978 - Properties of unusual phospholipids, ii: synthesis, nmr studies and monolayer investiga... 8443568 - The thiobarbituric acid assay reflects susceptibility to oxygen induced lipid peroxidat... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-12-19 |
Journal Detail:
|
Title: Biomaterials Volume: - ISSN: 1878-5905 ISO Abbreviation: Biomaterials Publication Date: 2012 Dec |
Date Detail:
|
Created Date: 2012-12-24 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
|
Copyright © 2012 Elsevier Ltd. All rights reserved. |
Affiliation:
|
The University of Texas at Austin, College of Pharmacy, Pharmaceutics Division, Austin, TX 78712, United States. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Melittin-grafted HPMA-oligolysine based copolymers for gene delivery.
Next Document: The effect of microgrooved culture substrates on calcium cycling of cardiac myocytes derived from hu...