Document Detail


Uptake and intracellular fate of disulfide-bonded polymer hydrogel capsules for Doxorubicin delivery to colorectal cancer cells.
MedLine Citation:
PMID:  20420377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Understanding the interactions between drug carriers and cells is of importance to enhance the delivery of therapeutics. The release of therapeutics into different intracellular environments, such as the lysosomes or the cell cytoplasm, will impact their pharmacological activity. Herein, we investigate the intracellular fate of layer-by-layer (LbL)-assembled, submicrometer-sized polymer hydrogel capsules in a human colon cancer derived cell line, LIM1899. The cellular uptake of the disulfide-stabilized poly(methacrylic acid) (PMA(SH)) capsules by colon cancer cells is a time-dependent process. Confocal laser scanning microscopy and transmission electron microscopy reveal that the internalized capsules are deformed in membrane-enclosed compartments, which further mature to late endosomes or lysosomes. We further demonstrate the utility of these redox-responsive PMA(SH) capsules for the delivery of doxorubicin (DOX) to colon cancer cells. The DOX-loaded PMA(SH) capsules demonstrate a 5000-fold enhanced cytotoxicity in cell viability studies compared to free DOX.
Authors:
Yan Yan; Angus P R Johnston; Sarah J Dodds; Marloes M J Kamphuis; Charles Ferguson; Robert G Parton; Edouard C Nice; Joan K Heath; Frank Caruso
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  ACS nano     Volume:  4     ISSN:  1936-086X     ISO Abbreviation:  ACS Nano     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-09-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101313589     Medline TA:  ACS Nano     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2928-36     Citation Subset:  IM    
Affiliation:
Department of Chemical and Biomolecular Engineering, The University of Melbourne, Centre for Nanoscience and Nanotechnology, Victoria 3010, Australia.
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MeSH Terms
Descriptor/Qualifier:
Biological Transport
Cell Line, Tumor
Cell Nucleus / metabolism
Colorectal Neoplasms / pathology*
Diffusion
Disulfides / chemistry
Doxorubicin / chemistry*,  metabolism,  pharmacology
Drug Carriers / chemistry*,  metabolism*
Endosomes / metabolism
Humans
Hydrogels / chemistry*
Hydrogen-Ion Concentration
Hydrophobicity
Intracellular Space / metabolism*
Lysosomes / metabolism
Particle Size
Polymers / chemistry*
Silicon Dioxide / chemistry
Chemical
Reg. No./Substance:
0/Disulfides; 0/Drug Carriers; 0/Hydrogels; 0/Polymers; 23214-92-8/Doxorubicin; 7631-86-9/Silicon Dioxide

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


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