AG Mailänder (III. Medizinische Klinik und Poliklinik)

Nanoparticles for Cellular Therapeutics

Arbeitsgruppe: III. Medizinische Klinik Univ.-Prof. Dr. Volker Mailänder 
Kooperationspartner: Prof. K. Landfester (MPI für Polymerforschung), Dr. K. Koynov (MPI für Polymerforschung), Prof. W. Herr/PD Dr. R. Meyer (III. Medizinische Klinik),

The combination of nanocarriers with human (stem) cells offers a plethora of possibilities for enhancing the effectiveness of cellular therapeutics. Herefore nanosized capsules between 10 and 300 nm are used as carriers for drugs and diagnostic substances (Mailänder et al. 2009). Interdisciplinary research projects in this area include the design and synthesis of functionalized biodegradable nanoparticles/nanocapsules for imaging in vivo, site specific drug delivery, and controlled release of a drug within the targeted cells.

The ability to modify specific features of their physical, chemical and biological properties opens the way to manipulate the actions of nanoparticles in biomedical applications. For example we have shown that elongated shapes have a major impact on the effectiveness of the uptake of nanoparticles into cells (Florez et al. 2012). We have investigated the contribution of different uptake mechanisms for the incorporation of nanoparticles into cells. While surface modifications with charged side groups alter the uptake behavior in different cell types specific uptake first needs the suppression of unspecific interactions with the non-target cells. Herefore we used hydroxyethyl starch based nanocapsules (Baier et al. 2012). In order to prove that they can be specifically targeted we grafted folic acid on these capsules and showed their uptake into receptor positive, but avoidance of uptake into receptor negative cell types.

Besides these parameters especially capsule thickness are critical parameters that can be varied. By enhancing the biodegradability at low pH (Siebert et al. 2012) a highly effective intracellular delivery can be achieved. We have been introducing peptide sequences into the polymeric structures of nanocapsules such that overexpressed enzymes in specific cells can trigger the release (Maier et al. 2011). Furthermore their behavior in plasma, blood and their uptake into cells as well as their distribution on a macro- and microscale is investigated in our group. All this enables us to specifically design nanocarriers for delivery of drugs and diagnostics to cells used in cellular therapeutics like stem cells or immune cells or in regenerative medicine where scaffolds are decorated with nanocarriers for a slow and sustained release of growth and differentiation factors. Furthermore these functionally enhanced scaffolds can be pre-seeded with cells ex vivo and then implanted in order to replace a diseased or injured tissue. This will lead to reliable regeneration of bone and cartilage, but also regeneration of skin can be achieved by these means. 

References

Baier G, Baumann D, Siebert JM, Musyanovych A, Mailänder V , Landfester  K.; Suppressing Unspecific Cell Uptake for Targeted Delivery Using Hydroxyethyl Starch Nanocapsules; Biomacromolecules 2012, 13, 2704-2715. 

Florez L, Herrmann C, Cramer JM, Hauser CP, Koynov, K, Landfester K,  Crespy D, Mailänder V; How Shape Influences Uptake: Interactions of Anisotropic Polymer Nanoparticles and Human Mesenchymal Stem Cells; Small  2012, 8, 2222-2230. 

Maier M, Kotman N, Friedrichs C, Andrieu J, Wagner M, Graf R, Strauss WSL, Mailänder, V, Weiss CK, Landfester K. Highly Site Specific, Protease Cleavable, Hydrophobic Peptide-Polymer Nanoparticles; Macromolecules 2011, 44, 6258-6267. 

Mailänder V, Landfester K.; Interaction of nanoparticles with cells;Biomacromolecules 2009 10, 2379-400. 

Siebert, JM, Baumann, D, Zeller, A, Mailänder, V, Landfester, K.; Synthesis of Polyester Nanoparticles in Miniemulsion Obtained by Radical Ring-Opening of BMDO and Their Potential as Biodegradable Drug Carriers. Macromol Biosci 2012,12, 165-175.