title: Uptake and intracellular fate of disulfide-bonded polymer hydrogel capsules for Doxorubicin delivery to colorectal cancer cells.
abstract: 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.affiliation: Department of Chemical and Biomolecular Engineering, The University of Melbourne, Centre for Nanoscience and Nanotechnology, Victoria 3010, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Dodds
authors.forename: Marloes M J
authors.initials: MM
authors.lastname: Kamphuis
authors.forename: Charles
authors.initials: C
authors.lastname: Ferguson
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Edouard C
authors.initials: EC
authors.lastname: Nice
authors.forename: Joan K
authors.initials: JK
authors.lastname: Heath
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000473:pathology*; D004058:Diffusion; D004220:Disulfides / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D020100:Hydrogels; D011108:Polymers; D012822:Silicon Dioxide; D004317:Doxorubicin