Uptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells

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 investig...

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Published in:ACS nano 2010-05, Vol.4 (5), p.2928-2936
Main Authors: Yan, Yan, Johnston, Angus P. R, Dodds, Sarah J, Kamphuis, Marloes M. J, Ferguson, Charles, Parton, Robert G, Nice, Edouard C, Heath, Joan K, Caruso, Frank
Format: Article
Language:English
Subjects:
Biological Transport
Cell Line, Tumor
Cell Nucleus - metabolism
Colorectal Neoplasms - pathology
Diffusion
Disulfides - chemistry
Doxorubicin - chemistry
Doxorubicin - metabolism
Doxorubicin - pharmacology
Drug Carriers - chemistry
Drug Carriers - metabolism
Endosomes - metabolism
Humans
Hydrogels - chemistry
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Intracellular Space - metabolism
Lysosomes - metabolism
Particle Size
Polymers - chemistry
Silicon Dioxide - chemistry
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Summary: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) (PMASH) 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 PMASH capsules for the delivery of doxorubicin (DOX) to colon cancer cells. The DOX-loaded PMASH capsules demonstrate a 5000-fold enhanced cytotoxicity in cell viability studies compared to free DOX.
ISSN:1936-0851
1936-086X
DOI:10.1021/nn100173h