International audienc

The uptake and release capacities of mesoporous silica particles are measured on nanovalve-gated stimulated release systems, using a water soluble biological stain, Hoechst 33342, as the cargo model. Five different types of mesoporous silica nanoparticles: 2D-hexagonal MCM-41, swollen pore MCM-41, rod-like MCM-41, hollow mesoporous nanoparticles and radial mesoporous nanoparticles are studied and compared. Solid silica nanoparticles are used as the control. Because of the presence of the nanovalves, the loaded and capped particles can be washed thoroughly without losing the content of the mesopores. The quantity of Hoechst 33342 molecules trapped within the nanoparticles and released upon opening the nanovalves are systematically studied for the first time. The loading conditions are optimized by varying the Hoechst concentration in the loading solutions. Surprisingly, increasing the Hoechst concentration in the loading solution does not always result in a larger amount of Hoechst being trapped and released. Among the five types of mesoporous silica nanoparticles, the radial mesoporous nanoparticles and the swollen pore MCM-41 particles show the highest and lowest release capacity, respectively. The uptake capacities is correlated with the specific surface area of the materials rather than their internal volume. The uptake and release behaviors are also affected by charge and spatial factors.

Dendritic cells (DC) are the most potent antigen-presenting cells and are fundamental for the establishment of transplant tolerance. The Dendritic Cell-Specific Intracellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN; CD209) receptor provides a target for dendritic cell therapy. Biodegradable and high-surface area porous silicon (pSi) nanoparticles displaying anti-DC-SIGN antibodies and loaded with the immunosuppressant rapamycin (Sirolimus) serve as a fit-for-purpose platform to target and modify DC. Here, we describe the fabrication of rapamycin-loaded DC-SIGN displaying pSi nanoparticles, the uptake efficiency into DC and the extent of nanoparticle-induced modulation of phenotype and function. DC-SIGN antibody displaying pSi nanoparticles favourably targeted and were phagocytosed by monocyte-derived and myeloid DC in whole human blood in a time- and dose-dependent manner. DC preconditioning with rapamycin-loaded nanoparticles, resulted in a maturation resistant phenotype and significantly suppressed allogeneic T-cell proliferation.