Novel nano-coating protects therapeutic proteins on medical devices from damage by conventional sterilization techniques
Component from liquorice helps to provide cleaner medical implants.|
A nanotech material also containing an extract from liquorice can be used to sterilize and protect medical devices and implants functionalized with biological components such as therapeutic proteins and antibodies and protects them during the sterilization process. Writing in the journal Materials Today, a team from Germany and Austria explains how conventional sterilization techniques based on a blast of radiation, or exposure to toxic gas can damage functional biological components of the device.
The coating, developed by the German biotech company LEUKOCARE AG, protects these sensitive components. Joachim Koch of the Georg-Speyer Haus, Institute for Biomedical Research in Frankfurt am Main in Germany and colleagues explain how medical devices and implants are increasingly functionalized using pharmacologically active proteins, antibodies and other biomolecules. Harsh sterilization procedures, including beta and gamma irradiation or exposure to toxic ethylene oxide can damage these sensitive molecules and render the device useless.
However, without sterilization the patient is at risk of infection when the device is used or implanted. The team has successfully evaluated the nano-coating. The technology employs a composition of stabilizing nano-molecules. One relevant ingredient is a compound known as glycyrrhizic acid, which is the natural sweet-tasting chemical in liquorice. Unlike other stabilizing approaches in biopharmaceutical formulations the nano-coating contains no sugars, sugar-alcohol compounds or proteins that might otherwise interfere with the biological activity of the device.
The team has tested the nano-coating by coupling and stabilizing an anti-inflammatory antibody, which may be used in therapy, to a porous polyurethane surface. This carrier acts as a surrogate for a medical device. Such a system might be used as a therapeutic implant to reduce inflammation caused by an overactive immune system in severely ill patients. The researchers found that even if the test device is blasted with radiation to sterilize it entirely, neither the nano-coating nor the proteins are damaged by the radiation and the activity of the device is maintained. "This nano-coating formulation can now be applied for the production of improved biofunctionalized medical devices such as bone implants, vascular stents, and wound dressings and will ease the application of biomedical combination products," Koch explains.
Fabrication process of a bio-functionalized surface and its protection from radiation mediated damage.
The chemical interactions between protein, water, and co-solutes are depicted schematically. Co-solvents provide hydrogen bonds and substitute for water molecules. (A) Surface with immobilized protein, (B) incubation with stabilizing co-solvent, (C) irradiation of dried surface, (D) rehydration, removal of co-solvent, (E) preferential hydration of protein and exclusion of co-solvent (grey ovals),
(F) stabilization of protein by hydrogen bonding to co-solvent molecules.
Tscheliessnig, R., Zörnig, M., Herzig, E. M., Lückerath, K., Altrichter, J., Kemter, K., Paunel-Görgülü, A., Lögters, T., Windolf, J., Pabisch, S., Cinatl, J., Rabenau, H. F., Jungbauer, A., Müller-Buschbaum, P., Scholz, M. and Koch, J. (2012) Nano-coating protects biofunctional materials. Materials Today, 15, 394-404.
Novel insights into recognition of tumor cells by natural killer cells of the innate immune system
The natural cytotoxicity receptors (NCRs) are a unique set of activating proteins expressed mainly on the surface of natural killer (NK) cells. The human NCR family is comprised of the three type I membrane proteins NKp30, NKp44, and NKp46. Especially NKp30 is critical for the cytotoxicity of NK cells against different targets, including tumor, virus-infected, and immature dendritic cells. Although the crystal structure of NKp30 was recently solved, a key question, how NKp30 recognizes several non-related ligands, remains unclear. Therefore, we investigated the parameters which impact on ligand recognition of NKp30. Based on various NKp30::hIgG1-Fc-fusion proteins, which were optimized for minimal background binding to cellular Fc-gamma receptors, we identified the flexible stalk region of NKp30 as an important, but so far neglected module, for ligand recognition and related signaling of the corresponding full-length receptor proteins. Moreover, we found that the ectodomain of NKp30 is N-linked glycosylated at three different sites. Mutational analyses revealed differential binding affinities and signaling capacities of mono-, di- or tri-glycosylated NKp30, suggesting that the degree of glycosylation could provide a switch to modulate the ligand-binding properties of NKp30 and NK cell cytotoxicity.