School of Chemistry - Research Publications

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Author: De Rose, Robert × Author: Kent, Stephen × Start date: 2009 × Type: Journal Article ×

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    Tuning the properties of pH responsive nanoparticles to control cellular interactions in vitro and ex vivo
    Mann, SK ; Dufour, A ; Glass, JJ ; De Rose, R ; Kent, SJ ; Such, GK ; Johnston, APR (ROYAL SOC CHEMISTRY, 2016-01-01)
    Engineering the properties of nanoparticles to limit non-specific cellular interactions is critical for developing effective drug delivery systems. Differences between interactions with cultured cells and human blood highlights the need for appropriate assays
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    Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies
    Cui, J ; Ju, Y ; Houston, ZH ; Class, JJ ; Fletcher, NL ; Alcantara, S ; Dai, Q ; Howard, CB ; Mahler, SM ; Wheatley, AK ; De Rose, R ; Brannon, PT ; Paterson, BM ; Donnelly, PS ; Thurecht, K ; Caruso, F ; Kent, SJ (WILEY, 2019-05)
    Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.
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    P17-03. Nanoengineered layer-by-layer capsules as a novel delivery system for HIV vaccines
    Sexton, A ; Whitney, PG ; De Rose, R ; Zelikin, AN ; Chong, S ; Johnston, AP ; Caruso, F ; Kent, SJ (Springer Science and Business Media LLC, 2009-10-22)
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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 Poly(ethylene glycol) Particles for Improved Biodistribution
    Cui, J ; De Rose, R ; Alt, K ; Alcantara, S ; Paterson, BM ; Liang, K ; Hu, M ; Richardson, JJ ; Yan, Y ; Jeffery, CM ; Price, RI ; Peter, K ; Hagemeyer, CE ; Donnelly, PS ; Kent, SJ ; Caruso, F (AMER CHEMICAL SOC, 2015-02)
    We report the engineering of poly(ethylene glycol) (PEG) hydrogel particles using a mesoporous silica (MS) templating method via tuning the PEG molecular weight, particle size, and the presence or absence of the template and investigate the cell association and biodistribution of these particles. An ex vivo assay based on human whole blood that is more sensitive and relevant than traditional cell-line based assays for predicting in vivo circulation behavior is introduced. The association of MS@PEG particles (template present) with granulocytes and monocytes is higher compared with PEG particles (template absent). Increasing the PEG molecular weight (from 10 to 40 kDa) or decreasing the PEG particle size (from 1400 to 150 nm) reduces phagocytic blood cell association of the PEG particles. Mice biodistribution studies show that the PEG particles exhibit extended circulation times (>12 h) compared with the MS@PEG particles and that the retention of smaller PEG particles (150 nm) in blood, when compared with larger PEG particles (>400 nm), is increased at least 4-fold at 12 h after injection. Our findings highlight the influence of unique aspects of polymer hydrogel particles on biological interactions. The reported PEG hydrogel particles represent a new class of polymer carriers with potential biomedical applications.