Biochemistry and Pharmacology - Research Publications

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Start date: 2010 × End date: 2011 × Author: JOHNSTON, ANGUS × Author: Heath, Joan × Type: Journal Article ×

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    Uptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells
    Yan, Y ; Johnston, APR ; Dodds, SJ ; Kamphuis, MMJ ; Ferguson, C ; Parton, RG ; Nice, EC ; Heath, JK ; Caruso, F (AMER CHEMICAL SOC, 2010-05)
    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.
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    Targeting of Cancer Cells Using Click-Functionalized Polymer Capsules
    Kamphuis, MMJ ; Johnston, APR ; Such, GK ; Dam, HH ; Evans, RA ; Scott, AM ; Nice, EC ; Heath, JK ; Caruso, F (AMER CHEMICAL SOC, 2010-11-17)
    Targeted delivery of drugs to specific cells allows a high therapeutic dose to be delivered to the target site with minimal harmful side effects. Combining targeting molecules with nanoengineered drug carriers, such as polymer capsules, micelles and polymersomes, has significant potential to improve the therapeutic delivery and index of a range of drugs. We present a general approach for functionalization of low-fouling, nanoengineered polymer capsules with antibodies using click chemistry. We demonstrate that antibody (Ab)-functionalized capsules specifically bind to colorectal cancer cells even when the target cells constitute less than 0.1% of the total cell population. This precise targeting offers promise for drug delivery applications.