Mucin-related carbohydrates are overexpressed on the surface of cancer cells, providing a disease-specific target for cancer immunotherapy. Here, we describe the design and construction of peptide-free multivalent glycosylated nanoscale constructs as potential synthetic cancer vaccines that generate significant titers of antibodies selective for aberrant mucin glycans. A polymerizable version of the Tn-antigen glycan was prepared and converted into well-defined glycopolymers by Reversible Addition–Fragmentation chain Transfer (RAFT) polymerization. The polymers were then conjugated to gold nanoparticles, yielding ‘multicopy-multivalent’ nanoscale glycoconjugates. Immunological studies indicated that these nanomaterials generated strong and long-lasting production of antibodies that are selective to the Tn-antigen glycan and cross-reactive toward mucin proteins displaying Tn. The results demonstrate proof-of-concept of a simple and modular approach toward synthetic anticancer vaccines based on multivalent glycosylated nanomaterials without the need for a typical vaccine protein component.

Sequence sets structure: Amphiphilic norbornene‐based double‐comb diblock polymers with peptide and oligo(ethylene oxide) side chains aggregate in water to form unprecedented complex morphologies depending on the amino acid sequence of the peptide. The internal structures of the aggregates observed by cryo electron tomography show densely folded and highly branched wormlike micelles (left) and spherical aggregates with a bicontinuous architecture (right).

The ring‐opening metathesis polymerizations (ROMP), using RuCl2 (PCy3)2CHPh, of a series of peptide‐functionalized norbornene derivatives have been investigated. Incorporation of a PEG‐monomer was found to prevent premature precipitation of polymer strands during the course of polymerization reactions and yield water compatible polymers in high conversions. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3178–3190, 2007

Zwitterionic chemical groups have well-documented resistance to marine fouling species when presented as homogeneous polymer brushes. These model formulations are not, however, suitable for practical fouling-control applications. It is presently unknown if a uniform film of zwitterions is required to elicit nonfouling character via the binding of interfacial water or if the incorporation of zwitterionic functionality into a more practical bulk polymer system will suffice. Here, copolymers of n-butyl methacrylate were synthesized with low incorporation levels (up to 20 mol %) of hydrophilic functionality, including zwitterionic moieties. Their antifouling (AF) properties were evaluated using barnacle cyprids (Balanus improvisus), diatom cells (Navicula incerta), and a multispecies biofilm. The laboratory assays revealed higher resistance of ionic copolymers toward cyprid settlement, which was attributed to their swelling and the presence of nonfreezable water molecules bound tightly to the polymer chains. Additionally, cells of N. incerta and the multispecies biofilm were removed more effectively on polymers containing sulfobetaine methacrylate and sulfopropyl methacrylate moieties. The results indicate that the presence of tightly bound interfacial water is not limited to model systems of pure hydrophilic homopolymers, but that this mechanism can also reduce the settlement and adhesion of fouling species via bulk copolymer systems with limited hydrophilic content. The swelling of polymers with hydrophilic content may also contribute to their AF efficacy, and such materials may therefore represent a route to translation of the well-documented nonfouling character of zwitterions into practical, industrially relevant coating formulations.

Die Sequenz bestimmt die Struktur: Amphiphile Doppelkamm‐Diblockcopolymere aus Norbornen mit Peptid‐ und Oligo(ethylenoxid)‐Seitenketten aggregieren in Wasser zu komplexen Strukturen, deren Morphologie von der Aminosäuresequenz des Peptids abhängt. Die innere Struktur der Aggregate wurde durch Kryo‐Elektronentomographie untersucht und zeigt dicht gefaltete, hochverzweigte wurmartige Micellen (links) und sphärische Aggregate mit bikontinuierlichem Aufbau (rechts).