School of Chemistry - Research Publications

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Type: Journal Article × Start date: 2010 × End date: 2019 × Author: Caruso, Francesco × Author: YAN, YAN × Author: OCHS, CHRISTOPHER ×

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    Immobilization and Intracellular Delivery of an Anticancer Drug Using Mussel-Inspired Polydopamine Capsules
    Cui, J ; Yan, Y ; Such, GK ; Liang, K ; Ochs, CJ ; Postma, A ; Caruso, F (AMER CHEMICAL SOC, 2012-08)
    We report a facile approach to immobilize pH-cleavable polymer-drug conjugates in mussel-inspired polydopamine (PDA) capsules for intracellular drug delivery. Our design takes advantage of the facile PDA coating to form capsules, the chemical reactivity of PDA films, and the acid-labile groups in polymer side chains for sustained pH-induced drug release. The anticancer drug doxorubicin (Dox) was conjugated to thiolated poly(methacrylic acid) (PMA(SH)) with a pH-cleavable hydrazone bond, and then immobilized in PDA capsules via robust thiol-catechol reactions between the polymer-drug conjugate and capsule walls. The loaded Dox showed limited release at physiological pH but significant release (over 85%) at endosomal/lysosomal pH. Cell viability assays showed that Dox-loaded PDA capsules enhanced the efficacy of eradicating HeLa cancer cells compared with free drug under the same assay conditions. The reported method provides a new platform for the application of stimuli-responsive PDA capsules as drug delivery systems.
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    Biodegradable Click Capsules with Engineered Drug-Loaded Multilayers
    Ochs, CJ ; Such, GK ; Yan, Y ; van Koeverden, MP ; Caruso, F (AMER CHEMICAL SOC, 2010-03)
    We report the modular assembly of a polymer-drug conjugate into covalently stabilized, responsive, biodegradable, and drug-loaded capsules with control over drug dose and position in the multilayer film. The cancer therapeutic, doxorubicin hydrochloride (DOX), was conjugated to alkyne-functionalized poly(l-glutamic acid) (PGA(Alk)) via amide bond formation. PGA(Alk) and PGA(Alk+DOX) were assembled via hydrogen bonding with poly(N-vinyl pyrrolidone) (PVPON) on planar and colloidal silica templates. The films were subsequently covalently stabilized using diazide cross-linkers, and PVPON was released from the multilayers by altering the solution pH to disrupt hydrogen bonding. After removal of the sacrificial template, single-component PGA(Alk) capsules were obtained and analyzed by optical microscopy, transmission electron microscopy, and atomic force microscopy. The PGA(Alk) capsules were stable in the pH range between 2 and 11 and exhibited reversible swelling/shrinking behavior. PGA(Alk+DOX) was assembled to form drug-loaded polymer capsules with control over drug dose and position in the multilayer system (e.g., DOX in every layer or exclusively in layer 3). The drug-loaded capsules could be degraded enzymatically, resulting in the sustained release of active DOX over approximately 2 h. Cellular uptake studies demonstrate that the viability of cells incubated with DOX-loaded PGA(Alk) capsules significantly decreased. The general applicability of this modular approach, in terms of incorporation of polymer-drug conjugates in other click multilayer systems, was also demonstrated. Biodegradable click capsules with drug-loaded multilayers are promising candidates as carrier systems for biomedical applications.
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    Bypassing Multidrug Resistance in Cancer Cells with Biodegradable Polymer Capsules
    Yan, Y ; Ochs, CJ ; Such, GK ; Heath, JK ; Nice, EC ; Caruso, F (WILEY-V C H VERLAG GMBH, 2010-12-14)