Document Detail


Multifunctional SPIO/DOX-loaded wormlike polymer vesicles for cancer therapy and MR imaging.
MedLine Citation:
PMID:  20828811     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Stable and tumor-targeting multifunctional wormlike polymer vesicles simultaneously loaded with superparamagnetic iron oxide (SPIO) nanoparticles (NPs) as magnetic resonance imaging (MRI) contrast agent and anticancer drug doxorubicin (DOX) were developed for targeted cancer therapy and ultrasensitive MR imaging. These multifunctional wormlike polymer vesicles were formed by heterobifunctional amphiphilic triblock copolymers R (R = methoxy or folate (FA))-PEG(114)-PLA(x)-PEG(46)-acrylate using a double emulsion method. The long PEG segments bearing methoxy/folate groups (CH(3)O/FA-PEG(114)) were mostly segregated to the outer hydrophilic PEG layers of the wormlike vesicles thereby providing active tumor-targeting ability, while the short PEG segments bearing acrylate groups (PEG(46)-acrylate) were mostly segregated onto the inner hydrophilic PEG layers of the wormlike vesicles thereby allowing the inner PEG layers to be crosslinked via free radical polymerization for enhanced in vivo stability. The hydrophobic anticancer drug, DOX, was loaded into the hydrophobic membrane of the wormlike vesicles. Meanwhile, a cluster of hydrophilic SPIO NPs was encapsulated into the aqueous cores of the stable wormlike vesicles with crosslinked inner PEG layers for ultrasensitive MRI detection. Cellular uptake of the FA-conjugated wormlike vesicles facilitated by the folate receptor-mediated endocytosis process was higher than that of the FA-free vesicles thereby leading to high cytotoxicity against the HeLa human cervical tumor cell line. Moreover, the SPIO/DOX-loaded wormlike vesicles with crosslinked inner PEG layers demonstrated a much higher r(2) relaxivity value than Feridex, a commercially available T(2) agent, which can be attributed to the high SPIO NPs loading level as well as the SPIO clustering effect. These unique stable and tumor-targeting multifunctional SPIO/DOX-loaded wormlike polymer vesicles would make targeted cancer theranostics possible thereby paving the road for personalized medicine.
Authors:
Xiaoqiang Yang; Jamison J Grailer; Ian J Rowland; Alireza Javadi; Samuel A Hurley; Douglas A Steeber; Shaoqin Gong
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-09-09
Journal Detail:
Title:  Biomaterials     Volume:  31     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  9065-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Mechanical Engineering, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Death / drug effects
Dextrans / chemistry*
Doxorubicin / pharmacology,  therapeutic use*
Drug Carriers / chemistry*
Drug Delivery Systems
Flow Cytometry
Folic Acid / pharmacology
Hela Cells
Humans
Hydrophobic and Hydrophilic Interactions / drug effects
Magnetic Resonance Imaging*
Magnetic Resonance Spectroscopy
Magnetite Nanoparticles / chemistry*
Microscopy, Confocal
Nanoparticles / ultrastructure
Neoplasms / drug therapy*
Polymers / chemical synthesis,  chemistry*
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Magnetite Nanoparticles; 0/Polymers; 119683-68-0/ferumoxides; 23214-92-8/Doxorubicin; 59-30-3/Folic Acid; 9004-54-0/Dextrans

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


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