Targeting cell populations via endogenous carbohydrate receptors is an appealing approach for drug delivery. However, to be effective, this strategy requires the production of high affinity carbohydrate ligands capable of engaging with specific cell-surface lectins. To develop materials that exhibit high affinity towards these receptors, we synthesized glycopolymers displaying pendant carbohydrate moieties from carbohydrate-functionalized monomer precursors via reversible addition-fragmentation chain transfer (RAFT) polymerization. These glycopolymers were fluorescently labeled and used to determine macrophage-specific targeting both in vitro and in vivo. Mannose- and N-acetylglucosamine-containing glycopolymers were shown to specifically target mouse bone marrow-derived macrophages (BMDMs) in vitro in a dose-dependent manner as compared to a galactose-containing glycopolymer (30- and 19-fold higher uptake, respectively). In addition, upon macrophage differentiation, the mannose glycopolymer exhibited enhanced uptake in M2-polarized macrophages, an anti-inflammatory macrophage phenotype prevalent in injured tissue. This carbohydrate-specific uptake was retained in vivo, as alveolar macrophages demonstrated 6-fold higher internalization of mannose glycopolymer, as compared to galactose, following intratracheal administration in mice. We have shown the successful synthesis of a class of functional RAFT glycopolymers capable of macrophage-type specific uptake both in vitro and in vivo, with significant implications for the design of future targeted drug delivery systems.
Nanoparticle technologies provide a powerful tool for the development of reagents for use in both therapeutic and diagnostic, or "theragnostic" biomedical applications. Two broad classes of particles are under development, viral and synthetic systems, each with their respective strengths and limitations. Here we adapt the phage lambda system to construct modular "designer" nanoparticles that blend these two approaches. We have constructed a variety of modified "decoration" proteins that allow site-specific modification of the shell with both protein and nonproteinaceous ligands including small molecules, carbohydrates, and synthetic display ligands. We show that the chimeric proteins can be used to simultaneously decorate the shell in a tunable surface density to afford particles that are physically homogeneous and that can be manufactured to display a variety of ligands in a defined composition. These designer nanoparticles set the stage for development of lambda as a theragnostic nanoparticle system.
Flexible and transparent gas-diffusion barriers have played an important role in recent years. The present study describes a flexible barrier film with a tailored architecture of cationic polyelectrolytes and clay/polymer nanoassemblies. Highly oriented and well-aligned barrier films were achieved by the consecutive absorption of flexible cationic polymer and anionic montmorillonite platelets. The experimental results showed that the layer-by-layer deposition of oppositely charged thin films containing self-assembled poly(vinyl alcohol) and montmorillonites improved their gas barrier characteristics based on the Ca degradation test, enhancing their optical transparency. This nanostructure, fabricated using a solution process, is useful in many applications, for example, flexible and moisture-free organic electronics. This simple and fast method is suitable for the mass coating of large surface areas, as required in industry.
Layer-by-layer (LBL) assembly, which uses electronic and ionic intermolecular bonding under nonvacuum conditions, is a promising technology for fabricating gas barrier films owing to its simple processing and easy formation of a multilayer structure. In this research, nanoclay-polymer multilayers of Na(+)-montmorillonite (Na-MMT) were fabricated. Particularly, the addition of AuCl3 on fabricated MMT layers caused a reaction with the surface silanol functional groups (Si-O-H) of the MMT platelets, resulting in the formation of Au2O3 on the MMT-polymer multilayers. The Au2O3 filled the vacancies between the MMT platelets and linked the MMT platelets together, thus forming a gas barrier film that reduced the water vapor transmission rate (WVTR) to 3.2 × 10(-3) g m(-2) day(-1). AuCl3-treated MMT-polymer multilayers thus have the potential to be utilized for manufacturing gas barrier films for flexible electronics on a large scale.
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