Nanoparticles have been extensively employed to deliver many drugs, including siRNA, for the treatment
of a variety of diseases, particularly cancer. Lately, there has been a great deal of effort to design nanoparticles
with materials that are able to respond to intrinsic or extrinsic stimuli for “on demand” delivery of siRNA.
These nanoparticles are able to trigger siRNA release upon different stimuli, such as a pH decrease, redox gradient,
enzyme, light, magnetic field, temperature, ultrasound or electric current. Frequently, the stimuli cause the
nanoparticles to undergo protonation, hydrolytic breakdown or phase transition for triggered release of siRNA, resulting
in decreased side effects and better therapeutic outcome. While studies have demonstrated efficient in vitro
and in vivo delivery, these “smart” nanoparticles have not yet reached the clinic. In this review, we address different
classes of nanoparticles, such as polyplexes, lipoplexes, liposomes, polymeric micelles, polymeric, lipid and inorganic nanoparticles,
that are able to respond to specific stimuli for siRNA triggered-release, emphasizing their application and discussing the latest advances.