Chemical and Biomolecular Engineering - Research Publications

Permanent URI for this collection

http://hdl.handle.net/11343/353

Filters

2012 3
Reset filters

Settings
Statistics
Citations
Author: Caruso, Francesco × Author: POSTMA, ALMAR × End date: 2012 × Start date: 2012 × Type: Journal Article ×

Search Results

Now showing 1 - 3 of 3
  • Item
    No Preview Available
    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.
  • Item
    No Preview Available
    Photoinitiated Alkyne-Azide Click and Radical Cross-Linking Reactions for the Patterning of PEG Hydrogels
    Chen, RT ; Marchesan, S ; Evans, RA ; Styan, KE ; Such, GK ; Postma, A ; McLean, KM ; Muir, BW ; Caruso, F (AMER CHEMICAL SOC, 2012-03)
    The photolithographical patterning of hydrogels based solely on the surface immobilization and cross-linking of alkyne-functionalized poly(ethylene glycol) (PEG-tetraalkyne) is described. Photogenerated radicals as well as UV absorption by a copper chelating ligand result in the photochemical redox reduction of Cu(II) to Cu(I). This catalyzes the alkyne-azide click reaction to graft the hydrogels onto an azide-functionalized plasma polymer (N(3)PP) film. The photogenerated radicals were also able to abstract hydrogen atoms from PEG-tetraalkyne to form poly(α-alkoxy) radicals. These radicals can initiate cross-linking by addition to the alkynes and intermolecular recombination to form the PEG hydrogels. Spatially controlling the two photoinitiated reactions by UV exposure through a photomask leads to surface patterned hydrogels, with thicknesses that were tunable from tens to several hundreds of nanometers. The patterned PEG hydrogels (ca. 60 μm wide lines) were capable of resisting the attachment of L929 mouse fibroblast cells, resulting in surfaces with spatially controlled cell attachment. The patterned hydrogel surface also demonstrated spatially resolved chemical functionality, as postsynthetic modification of the hydrogels was successfully carried out with azide-functionalized fluorescent dyes via subsequent alkyne-azide click reactions.
  • Item
    Thumbnail Image
    Macromolecule Functionalization of Disulfide-Bonded Polymer Hydrogel Capsules and Cancer Cell Targeting
    Shimoni, O ; Postma, A ; Yan, Y ; Scott, AM ; Heath, JK ; Nice, EC ; Zelikin, AN ; Caruso, F (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.