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

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; AlemaniaFil: Prozeller, Domenik. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Pereira, Jorge. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Simon, Johanna. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Han, Shen. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Wirsching, Sebastian. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Fichter, Michael. Johannes Gutenberg Universitat Mainz; AlemaniaFil: 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; AlemaniaFil: Lieberwirth, Ingo. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Morsbach, Svenja. Max-Planck-Institut für Polymerforschung; AlemaniaFil: Mailänder, Volker. Max-Planck-Institut für Polymerforschung; Alemania. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Gehring, Stephan. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Crespy, Daniel. Max-Planck-Institut für Polymerforschung; Alemania. Vidyasirimedhi Institute of Science and Technology; TailandiaFil: Landfester, Katharina. Max-Planck-Institut für Polymerforschung; Alemani

Applications of isothermal titration calorimetry in pure and applied research from 2016 to 2020

The last 5 years have seen a series of advances in the application of isothermal titration microcalorimetry (ITC) and interpretation of ITC data. ITC has played an invaluable role in understanding multiprotein complex formation including proteolysis-targeting chimeras (PROTACS), and mitochondrial autophagy receptor Nix interaction with LC3 and GABARAP. It has also helped elucidate complex allosteric communication in protein complexes like trp RNA-binding attenuation protein (TRAP) complex. Advances in kinetics analysis have enabled the calculation of kinetic rate constants from pre-existing ITC data sets. Diverse strategies have also been developed to study enzyme kinetics and enzyme-inhibitor interactions. ITC has also been applied to study small molecule solvent and solute interactions involved in extraction, separation, and purification applications including liquid-liquid separation and extractive distillation. Diverse applications of ITC have been developed from the analysis of protein instability at different temperatures, determination of enzyme kinetics in suspensions of living cells to the adsorption of uremic toxins from aqueous streams