Stimuli-Responsive Nanomachines and Caps for Drug Delivery.

In this review we focus on methods that are used to trap and release on command therapeutic drugs from mesoporous silica nanoparticles (MSNs). The pores in the MSNs are large enough to accommodate a wide range of cargo molecules such as anticancer and antibiotic drugs and yet small enough to be blocked by a variety of bulky molecules that act as caps. The caps are designed to be tightly attached to the pore openings and trap the cargo molecules without leakage, but upon application of a designed stimulus detach from the nanoparticles and release the cargo. Of special emphasis in this review are nanomachines that respond to stimuli administered from external sources such as light or magnetic fields, or from chemical stimuli produced by the biological system such as a general change in pH or redox potential, or a highly specific chemical produced by a cancer cell or infectious bacterium. The goal is to release a high local concentration of the cargo only where and when it is needed, thus minimizing off-target side effects. We discuss sophisticated reversible nanomachines but also discuss some useful caps that simply break off from the nanoparticles in response to the selected stimulus. Many ingenious systems have been and are being designed; we primarily highlight those that have been demonstrated to operate in vitro and/or in vivo. In most cases the closed MSNs are endocytosed by diseased or infected cells and opened inside the cells to release the drugs. We begin with an overview of the nanoparticles and nanomachines and then present examples of drug release triggered by internal chemical stimuli from the organism and finally by external light and magnetic field stimuli.