| Affiliation: | 1. EMBL Heidelberg, Genome Biology Unit, Meyerhofstraße 1, 69117 Heidelberg, Germany Max Planck Institute for Medical Research, Department of Cellular Biophysics and Central Scientific Facility “Cellular Biotechnology”, Jahnstr. 29, 69120 Heidelberg, Germany;2. Laboratory of Hematology and Immunology and Labor für Myelomforschung, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, Jette, 1090 Belgium;3. Universitätsklinikum Heidelberg, Medizinische Klinik V, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany;4. Max Planck Institute for Medical Research, Department of Cellular Biophysics and Central Scientific Facility “Cellular Biotechnology”, Jahnstr. 29, 69120 Heidelberg, Germany;5. Leibniz-Institut für Polymerforschung Dresden e.V., Abteilung Funktionale Kolloidale Materialien, Hohe Straße 6, 01069 Dresden, Germany |
| Abstract: | In the malignant plasma cell disease multiple myeloma (MM), bone lesions and resulting fractures caused by MM cell (MMC) accumulation represent a major cause of morbidity and mortality. Despite recent advantages in systemic treatment, residual MMCs remain, especially in bone lesions. Therefore an interfacial delivery system for local treatment of MM and induced bone disease based on polyelectrolyte complex nanoparticles (PEC NP) loaded with bone morphogenetic protein 6 (BMP-6) inducing de-novo bone formation and MMC apoptosis is presented herein. BMP-6 loaded PEC NP are fabricated by defined mixing bio-related cationic and anionic polysaccharides and BMP-6 according to molar ratio of BMP-6/PEC-NP of 1/3. BMP-6/PEC NP bound to a model substrate releases 10% BMP-6 sustainably within two weeks as accessed by infrared spectroscopy. BMP-6 loaded PEC NP adheres to cell membranes of MMCs and MSCs and activated phosphorylation of Smad 1/5. Osteogenic differentiation (ALP-concentration) is enhanced in MSCs (p < 0.05). All patient samples (10/10) of MMCs show significant induction of apoptosis (median 84%, p < 0.05). Finally, BMP-6/PEC NP are successfully integrated in a commercial hyaluronic acid based hydrogel material revealing MMC death as principal proof for the local treatment of MM induced bone lesions. |
