Document Detail


Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro.
MedLine Citation:
PMID:  21277920     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Multidrug resistance (MDR) is characterized by the overexpression of ATP-binding cassette (ABC) transporters that actively pump a broad class of hydrophobic chemotherapeutic drugs out of cancer cells. MDR is a major mechanism of treatment resistance in a variety of human tumors, and clinically applicable strategies to circumvent MDR remain to be characterized. Here we describe the fabrication and characterization of a drug-loaded iron oxide nanoparticle designed to circumvent MDR. Doxorubicin (DOX), an anthracycline antibiotic commonly used in cancer chemotherapy and substrate for ABC-mediated drug efflux, was covalently bound to polyethylenimine via a pH sensitive hydrazone linkage and conjugated to an iron oxide nanoparticle coated with amine terminated polyethylene glycol. Drug loading, physiochemical properties and pH lability of the DOX-hydrazone linkage were evaluated in vitro. Nanoparticle uptake, retention, and dose-dependent effects on viability were compared in wild-type and DOX-resistant ABC transporter over-expressing rat glioma C6 cells. We found that DOX release from nanoparticles was greatest at acidic pH, indicative of cleavage of the hydrazone linkage. DOX-conjugated nanoparticles were readily taken up by wild-type and drug-resistant cells. In contrast to free drug, DOX-conjugated nanoparticles persisted in drug-resistant cells, indicating that they were not subject to drug efflux. Greater retention of DOX-conjugated nanoparticles was accompanied by reduction of viability relative to cells treated with free drug. Our results suggest that DOX-conjugated nanoparticles could improve the efficacy of chemotherapy by circumventing MDR.
Authors:
Forrest M Kievit; Freddy Y Wang; Chen Fang; Hyejung Mok; Kui Wang; John R Silber; Richard G Ellenbogen; Miqin Zhang
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-01-26
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  152     ISSN:  1873-4995     ISO Abbreviation:  J Control Release     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-06-07     Completed Date:  2011-10-19     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  76-83     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antibiotics, Antineoplastic / administration & dosage*
Brain Neoplasms / drug therapy*
Cell Line, Tumor
Doxorubicin / administration & dosage*,  chemistry,  pharmacokinetics
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Ferric Compounds / administration & dosage*,  chemistry
Glioma / drug therapy*
Hydrogen-Ion Concentration
Metal Nanoparticles / administration & dosage*,  chemistry
Particle Size
Polyethylene Glycols / chemistry
Polyethyleneimine / chemistry
Rats
Solubility
Tissue Distribution
Grant Support
ID/Acronym/Agency:
R01 CA119408/CA/NCI NIH HHS; R01 CA119408-04/CA/NCI NIH HHS; R01 CA119408-04S1/CA/NCI NIH HHS; R01 EB006043/EB/NIBIB NIH HHS; R01 EB006043-03S1/EB/NIBIB NIH HHS; R01 EB006043-04/EB/NIBIB NIH HHS; R01CA119408/CA/NCI NIH HHS; R01EB006043/EB/NIBIB NIH HHS; T32 CA138312/CA/NCI NIH HHS; T32 CA138312-02/CA/NCI NIH HHS; T32CA138312/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Ferric Compounds; 0/Polyethylene Glycols; 1309-37-1/ferric oxide; 80168379AG/Doxorubicin; 9002-98-6/Polyethyleneimine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Ultrasound-mediated tumor imaging and nanotherapy using drug loaded, block copolymer stabilized perf...
Next Document:  Substrates for cardiovascular tissue engineering.