6533b85ffe1ef96bd12c25cb

RESEARCH PRODUCT

Controlling protein interactions in blood for effective liver immunosuppressive therapy by silica nanocapsules

subject

description

Immunosuppression with glucocorticoids is a common treatment for autoimmune liver diseases and after liver transplant, which is however associated with severe side-effects. Targeted delivery of glucocorticoids to inflammatory cells, e.g. liver macrophages and Kupffer cells, is a promising approach for minimizing side effects. Herein, we prepare core–shell silica nanocapsules (SiO2 NCs) via a sol–gel process confined in nanodroplets for targeted delivery of dexamethasone (DXM) for liver immunosuppressive therapy. DXM with concentrations up to 100 mg mL−1 in olive oil are encapsulated while encapsulation efficiency remains over 95% after 15 days. Internalization of NCs by non-parenchymal murine liver cells significantly reduces the release of inflammatory cytokines, indicating an effective suppression of inflammatory response of liver macrophages. Fluorescent and magnetic labeling of the NCs allows for monitoring their intracellular trafficking and biodegradation. Controlled interaction with blood proteins and good colloidal stability in blood plasma are achieved via PEGylation of the NCs. Specific proteins responsible for stealth effect, such as apolipoprotein A-I, apolipoprotein A-IV, and clusterin, are present in large amounts on the PEGylated NCs. In vivo biodistribution investigations prove an efficient accumulation of NCs in the liver, underlining the suitability of the SiO2 NCs as a dexamethasone carrier for treating inflammatory liver diseases. Fil: Jiang, Shuai. Max-Planck-Institut für Polymerforschung; Alemania Fil: Prozeller, Domenik. Max-Planck-Institut für Polymerforschung; Alemania Fil: Pereira, Jorge. Max-Planck-Institut für Polymerforschung; Alemania Fil: Simon, Johanna. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; Alemania Fil: Han, Shen. Max-Planck-Institut für Polymerforschung; Alemania Fil: Wirsching, Sebastian. Johannes Gutenberg Universitat Mainz; Alemania Fil: Fichter, Michael. Johannes Gutenberg Universitat Mainz; Alemania Fil: Mottola, Milagro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentina. Max-Planck-Institut für Polymerforschung; Alemania Fil: Lieberwirth, Ingo. Max-Planck-Institut für Polymerforschung; Alemania Fil: Morsbach, Svenja. Max-Planck-Institut für Polymerforschung; Alemania Fil: Mailänder, Volker. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; Alemania Fil: Gehring, Stephan. Johannes Gutenberg Universitat Mainz; Alemania Fil: Crespy, Daniel. Max-Planck-Institut für Polymerforschung; Alemania. Vidyasirimedhi Institute of Science and Technology; Tailandia Fil: Landfester, Katharina. Max-Planck-Institut für Polymerforschung; Alemania