There is tremendous current interest in using nanoparticles to deliver biomolecules and macromolecules (e.g., drugs and DNA) to specific sites in living systems. Release of the biomedical payload from the nanoparticle can be accomplished by chemical or enzymatic degradation of the nanoparticle or of the link between the payload and the nanoparticle. We are exploring an alternative payload-release strategy that builds on our work on template-synthesized nano test tubes. These are hollow nanotubes that are closed on one end and open on the other, and the dimensions can be controlled at will. If these nano test tubes could be filled with a payload and then the open end corked with a chemically labile cap, they might function as a universal delivery vehicle. We show here that silica nano test tubes can be covalently corked by chemical self-assembly of nanoparticles to the tubes. We also show that the nanoparticle corks remain attached to the mouths of the nano test tubes after liberation from the alumina template. For this proof-of-principle study, we used simple imine linkages to attach the corks to the test tubes. Schiff's bases are thermodynamically unstable in the presence of water; however, the multiple points of contact between the nano test tubes and nanoparticles allow the assembled structure to be metastable under our experimental conditions. Other chemical linkageseither more or less stablemay be more appropriate for other applications, and these are currently under development. Copyright © 2006 American Chemical Society.