Chemical and Biomolecular Engineering - Research Publications
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ItemUptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells(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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ItemEncapsulation of Water-Insoluble Drugs in Polymer Capsules Prepared Using Mesoporous Silica Templates for Intracellular Drug Delivery(WILEY-V C H VERLAG GMBH, 2010-10-08)
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ItemCapsosomes with Multilayered Subcompartments: Assembly and Loading with Hydrophobic Cargo(WILEY-V C H VERLAG GMBH, 2010-01-08)Abstract Therapeutic artificial cells or organelles are nanoengineered vehicles that are expected to substitute for missing or lost cellular function. The creation of capsosomes, polymer carrier capsules containing liposomal subcompartments, is a promising approach towards constructing such therapeutic devices using the layer‐by‐layer assembly method. Herein, the assembly of intact, nonaggregated capsosomes containing multiple liposome layers is reported. It is also further demonstrated that thiocoraline, a hydrophobic model peptide with antitumor activity, can be efficiently loaded into the membrane of the liposomal subcompartments of the capsosomes. Cell viability assays verify the activity of the trapped antitumor cargo. It is also shown that pristine capsosomes do not display inherent cytotoxic effects. The ability to tune the number of liposome layers and hence the drug loading in capsosomes as well as their noncytotoxicity provide new opportunities for the creation of therapeutic artificial cells and organelles.
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ItemBypassing Multidrug Resistance in Cancer Cells with Biodegradable Polymer Capsules(WILEY-V C H VERLAG GMBH, 2010-12-14)
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ItemCellular Association and Cargo Release of Redox-Responsive Polymer Capsules Mediated by Exofacial Thiols(WILEY-V C H VERLAG GMBH, 2011-09-08)
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ItemMacromolecule Functionalization of Disulfide-Bonded Polymer Hydrogel Capsules and Cancer Cell Targeting(AMER CHEMICAL SOC, 2012-02)We present a generic and versatile method for functionalization of disulfide-stabilized PMA hydrogel capsules (HCs) with macromolecules, including a number of specific antibodies to cancer cells. Functionalization was achieved by reversible addition-fragmentation chain transfer (RAFT) polymerization of poly(N-vinyl pyrrolidone) (PVPON), which introduced biorelevant heterotelechelic end groups (thiol and amine) to the polymer chain. The PVPON with heterotelechelic end groups was conjugated to the outermost layer of PMA HCs through the thiol groups and reacted with biotin via the amine groups to generate PMA/PVPON(biotin) HCs. On the basis of the high specific interaction and high affinity between biotin and avidin, and its derivates, such as NeutrAvidin (NAv), we functionalized the PMA HCs with biotinylated antibodies. We demonstrate significantly enhanced cellular binding and internalization of the antibody (Ab)-functionalized capsules compared with control human immunoglobulin (IgG)-functionalized capsules, suggesting these capsules can specifically interact with cells through antibody/antigen recognition. We anticipate that the versatility of the functionalization approach reported in this study will assist in targeted therapeutic delivery applications.