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Nanocarrier for Diagnostics and Therapy

Membrane Vesicles in Mistletoe Extracts, and the Encapsulation of Mistletoe Lectins

Mistletoepreparations are usedfor tumor therapy.While low-dose immunostimulating mistletoe agents have thus far not shown significantly positiveresults, the application of high-dosepreparations impresses with considerable therapeutic success. This could be dueto the fact that, in the preparation of mistletoe preparations, vesicles are formed from the plant's cell membranes that may in vivo be able to deliver active agents into the tumor ina manner similar to liposomes. These active agents include mistletoe lectinsas well as viscotoxins. In her PhD thesis, Dr. Karin Winkler looked in greater detail at the structure of the aforementioned vesicles and their interaction with the ingredients. Subsequently, in their PhD theses, Dr. Vanessa Bunjesand, Dr. Annette Steinbach in a collaborative effort with Dr. Gero Leneweit, Carl Gustav Carus Institute, Niefern-Öschelbronn, Germany (DFG 2007-2011) encapsulated mistletoe lectinI within liposomes with regard to future therapeutic applications; in addition, the protein's B chain was coupled to the liposomal surface for serving as a homing device.

Funding
This project was funded by the German Research Foundation (DFG) from 2007 to 2011.

 

Manojlovic V, Winkler K, Bunjes V, Neub A, Schubert R, Bugarski B, Leneweit G: Membrane interactions of ternary phospholipid/cholesterol bilayers and encapsulation efficiencies of a RIP II protein, Colloids and Surfaces B 64, 284-296, 2008. [zum Originalartikel]

Winkler K, Jäger S, Leneweit G, Schubert R: Interactions of viscotoxins with vesicles of genuine plant membranes, Planta Med. 74, 163-167, 2008. [Epub]

Winkler K, Leneweit G, Schubert R: Characterization of membrane vesicles in plant extracts, Colloids and Surfaces B 45, 57-65, 2005. [Epub]

 

Liposomes for Treating Chronic Granulomatous Disease

For treating chronic granulomatous disease (CGD), liposomes have been developed that, upon intravenous injection, are able to address certain types of blood-borne immune cells (i.e., granulocytes and monocytes) as well as macrophages in various organs. CGD is a hereditary disease in which the patients' immune cells suffer from an enzyme defect that renders them incapable to produce reactive oxygen species that play a major role in killing infectious pathogens. As a result, the courses of infection in patients affected with CGD - most of them children - are much more severe than in otherwise healthy people. In our treatment approach liposomally encapsulated glucose oxidase is delivered to the immune cells enabling the intracellular formation of hydrogen peroxide. Thus, the cell is provided with the main precursor of reactive oxygen species, the formation of which is impaired in the case of CGD patients. The most promising course of in-vitro experiments with isolated cells (PhD theses by Dr. Ulrike Falk, Dr. Andrea Kimpfler and Dr. Markus Gantert) let us hope that this approach may eventually reach a degree of maturity that will warrant clinical application. The glucose-oxidase / liposome project has been conducted in collaboration with the University's Children's Hospital, Tübingen, Germany (Professor Dr. Gernot Bruchelt, Dr. Claudia Gerber).

Funding
This project has been supported by the Reinhold Beitlich Foundation of the Fortüne Program, Tübingen, Germany, as well as - from 2003 to 2006 - by the German Research Council (DFG).

 

Gerber CE, Bruchelt G, Falk UB, Kimpfler A, Hauschild S, Kuçi S, Bächi T, Niethammer D, Schubert R: Reconstitution of bactericidal activity in cronic granulomatous disease cells by glucose-oxidase-containing liposomes, Blood 98, 3097-3105, 2001. [Epub]

 

Patent Blue Liposomes for Diagnostic Applications

Metastases dissiminated from malignant solid tumors first occur in the surrounding lymph nodes, and especially in the so-called sentinel lymph nodes. In order to diagnose the severity of the malignancy - such as in breast cancer - these lymph nodes are thus removed in the course of surgical intervention, and are pathologically examined for the presence of metastases. To identify the lymph nodes in the tumor-surrounding tissues, we have developed liposomes that contain the blue dye Patent Blue-Violet (PhD theses by Dr. Martin Werner and Dr. Andreas Fritze). The development of Patent-Blue liposomes was carried out together with Professor Dr. Peter Hirnle of the Universities of Tübingen and Bielefeld (both Germany).

 

Dieter M, Schubert R, Hirnle P: Blue liposomes for identification of the sentinel lymph nodes in pigs, Lymphology 36, 39-47, 2003. [Epub]

Hirnle P, Schubert R: Liposomes containing blue dye for preoperative lymph node staining: Distribution and stability in dogs after endolymphatic injection, Int. J. Pharm. 72, 259-269, 1991. [Epub]

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