Porous silicon nanoparticles (PSiNPs) were synthesized by silver-assisted electroless chemical etching of silicon nanowires generated on a silicon wafer. The rod-shaped particles (200-400 nm long and 100-200 nm in diameter) were derivatized with a cyclodextrin-based nano-valve that was closed at the physiological pH of 7.4 but open at pH <6. Release profiles in water and tissue culture media showed that no cargo leaked when the valves were closed and that release occurred immediately after acidification. In vitro studies using human pancreatic carcinoma PANC-1 cells proved that these PSiNPs were endocytosed and carried cargo molecules into the cells and released them in response to lysosomal acidity. These studies show that PSiNPs can serve as an autonomously functioning delivery platform in biological systems and open new possibilities for drug delivery.