School of Chemistry - Research Publications
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ItemNo Preview AvailableP17-03. Nanoengineered layer-by-layer capsules as a novel delivery system for HIV vaccines(Springer Science and Business Media LLC, 2009-10-22)
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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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ItemTargeting of Cancer Cells Using Click-Functionalized Polymer Capsules(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.
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ItemToward Therapeutic Delivery with Layer-by-Layer Engineered Particles(AMER CHEMICAL SOC, 2011-06)Layer-by-layer (LbL)-engineered particles have recently emerged as a promising class of materials for applications in biomedicine, with studies progressing from in vitro to in vivo. The versatility of LbL assembly coupled with particle templating has led to engineered particles with specific properties (e.g., stimuli-responsive, high cargo encapsulation efficiency, targeting), thus offering new opportunities in targeted and triggered therapeutic release. This Perspective highlights an important development by Poon et al. on tumor targeting in vivo using LbL-engineered nanoparticles containing a pH-responsive poly(ethylene glycol) (PEG) surface layer. Further, we summarize recent progress in the application of LbL particles in the fields of drug, gene, and vaccine delivery and cancer imaging. Finally, we explore future directions in this field, focusing on the biological processing of LbL-assembled particles.
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ItemPolymersome-Loaded Capsules for Controlled Release of DNA(WILEY-V C H VERLAG GMBH, 2011-07-18)The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but transitions to unimeric polymer chains upon acidification to cellular endocytic pH. These polymersomes can thus release an encapsulated payload in response to a change in pH from physiological to endocytic conditions. Multicomponent layer-by-layer capsules are formed by exploiting the ability of tannic acid to act as an efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA payload encapsulated within the polymersome subcompartments in response to changes in pH between physiological and endocytic conditions.
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ItemChallenges facing colloidal delivery systems: From synthesis to the clinic(ELSEVIER SCIENCE LONDON, 2011-06)
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ItemEngineering Particles for Therapeutic Delivery: Prospects and Challenges(AMER CHEMICAL SOC, 2012-05)Nanoengineered particles that can facilitate drug formulation and passively target tumors have reached the clinic in recent years. These early successes have driven a new wave of significant innovation in the generation of advanced particles. Recent developments in enabling technologies and chemistries have led to control over key particle properties, including surface functionality, size, shape, and rigidity. Combining these advances with the rapid developments in the discovery of many disease-related characteristics now offers new opportunities for improving particle specificity for targeted therapy. In this Perspective, we summarize recent progress in particle-based therapeutic delivery and discuss important concepts in particle design and biological barriers for developing the next generation of particles.
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ItemMechanically Tunable, Self-Adjuvanting Nanoengineered Polypeptide Particles(WILEY-V C H VERLAG GMBH, 2013-07-05)DNA-loaded polypeptide particles are prepared via templated assembly of mesoporous silica for the delivery of adjuvants. The elasticity and cargo-loading capacity of the obtained particles can be tuned by the amount of cross-linker used to stabilize the polypeptide particles. The use of polypeptide particles as biocarriers provides a promising method for vaccine delivery.
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ItemTargeting Cancer Cells: Controlling the Binding and Internalization of Antibody-Functionalized Capsules(AMER CHEMICAL SOC, 2012-08)The development of nanoengineered particles, such as polymersomes, liposomes, and polymer capsules, has the potential to offer significant advances in vaccine and cancer therapy. However, the effectiveness of these carriers has the potential to be greatly improved if they can be specifically delivered to target cells. We describe a general method for functionalizing nanoengineered polymer capsules with antibodies using click chemistry and investigate their interaction with cancer cells in vitro. The binding efficiency to cells was found to be dependent on both the capsule-to-cell ratio and the density of antibody on the capsule surface. In mixed cell populations, more than 90% of target cells bound capsules when the capsule-to-target cell ratio was 1:1. Strikingly, greater than 50% of target cells exhibited capsules on the cell surface even when the target cells were present as less than 0.1% of the total cell population. Imaging flow cytometry was used to quantify the internalization of the capsules, and the target cells were found to internalize capsules efficiently. However, the role of the antibody in this process was determined to enhance accumulation of capsules on the cell surface rather than promote endocytosis. This represents a significant finding, as this is the first study into the role antibodies play in internalization of such capsules. It also opens up the possibility of targeting these capsules to cancer cells using targeting molecules that do not trigger an endocytic pathway. We envisage that this approach will be generally applicable to the specific targeting of a variety of nanoengineered materials to cells.
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ItemEndocytic pH-Triggered Degradation of Nanoengineered Multilayer Capsules(WILEY-V C H VERLAG GMBH, 2014-03)The synthesis of cross-linker free layer-by-layer (LbL) capsules that solely utilize cellular pH variations as a trigger to specifically deconstruct and subsequently release cargo in cells is reported. These capsules demonstrate retention of water-soluble therapeutic molecules as small as 500 Da at extracellular pH. Triggered capsule degradation and release of cargo is observed within 30 min of cell uptake.