Biochemistry and Pharmacology - Research Publications

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Author: Cui, Jiwei × Author: JOHNSTON, ANGUS ×

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    Mechanically Tunable, Self-Adjuvanting Nanoengineered Polypeptide Particles
    Cui, J ; De Rose, R ; Best, JP ; Johnston, APR ; Alcantara, S ; Liang, K ; Such, GK ; Kent, SJ ; Caruso, F (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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    Engineering Enzyme-Cleavable Hybrid Click Capsules with a pH-Sheddable Coating for Intracellular Degradation
    Gunawan, ST ; Liang, K ; Such, GK ; Johnston, APR ; Leung, MKM ; Cui, J ; Caruso, F (WILEY-V C H VERLAG GMBH, 2014-10-29)
    The engineering of layer-by-layer (LbL) hybrid click capsules that are responsive to biological stimuli is reported. The capsules comprise a pH-sheddable, non cross-linked outer coating that protects enzyme-cleavable inner layers. Upon cellular uptake, the outer coating is released and the capsules are enzymatically degraded. In vitro cell degradation results in rapid capsule degradation (10 min) upon cellular internalization.
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    Endocytic pH-Triggered Degradation of Nanoengineered Multilayer Capsules
    Liang, K ; Such, GK ; Johnston, APR ; Zhu, Z ; Ejima, H ; Richardson, JJ ; Cui, J ; Caruso, F (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.
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    Tuning Particle Biodegradation through Polymer-Peptide Blend Composition
    Gunawan, ST ; Kempe, K ; Such, GK ; Cui, J ; Liang, K ; Richardson, JJ ; Johnston, APR ; Caruso, F (AMER CHEMICAL SOC, 2014-12)
    We report the preparation of polymer-peptide blend replica particles via the mesoporous silica (MS) templated assembly of poly(ethylene glycol)-block-poly(2-diisopropylaminoethyl methacrylate-co-2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl methacrylate) (PEG45-b-P(DPA55-co-PgTEGMA4)) and poly(l-histidine) (PHis). PEG45-b-P(DPA55-co-PgTEGMA4) was synthesized by atom transfer radical polymerization (ATRP), and was coinfiltrated with PHis into poly(methacrylic acid) (PMA)-coated MS particles assembled from different peptide-to-polymer ratios (1:1, 1:5, 1:10, or 1:15). Subsequent removal of the sacrificial templates and PMA resulted in monodisperse, colloidally stable, noncovalently cross-linked polymer-peptide blend replica particles that were stabilized by a combination of hydrophobic interactions between the PDPA and the PHis, hydrogen bonding between the PEG and PHis backbone, and π-π stacking of the imidazole rings of PHis side chains at physiological pH (pH ∼ 7.4). The synergistic charge-switchable properties of PDPA and PHis, and the enzymatic degradability of PHis, make these particles responsive to pH and enzymes. In vitro studies, in simulated endosomal conditions and inside cells, demonstrated that particle degradation kinetics could be engineered (from 2 to 8 h inside dendritic cells) based on simple adjustment of the peptide-to-polymer ratio used.