Glutathione-mediated intracellular release of anti-inflammatory N-acetyl-L-cysteine from mesoporous silica nanoparticles

We report on a smart mesoporous silica nanoparticle (MSN) that can trigger the release of anti-inflammatory N-acetyl-L-cysteine (NAC) within the intracellular environment. NAC was conjugated to the pore surfaces of MSNs through glutathione (GSH)-cleavable disulfide linkages. Solid-state nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, and Brunauer-Emmett-Teller (BET) analyses confirmed the successful NAC conjugation to the pore walls. The release of NAC from the NAC-conjugated MSN (MSN-NAC) could be controlled by adjusting the concentration of GSH regarding the release media. At an extracellular level of GSH (10 μM), the NAC release was greatly inhibited, whereas, at an intracellular level of GSH (2 mM), MSN-NAC facilitated the release of NAC. Confocal laser scanning microscopy (CLSM) studies showed that the NAC release was effectively triggered by intracellular GSH after uptake by BV-2 microglial cells. The MSN developed in this work may serve as the efficient intracellular carriers of NAC for the treatment of neuroinflammation. [graphic not available: see fulltext]