Abstract
Polymeric materials that respond to a variety of endogenous and external stimuli are actively developed to overcome the main barriers to successful systemic delivery of therapeutic nucleic acids. Here, an overview of viable stimuli that are proved to improve systemic delivery of nucleic acids is provided. The main focus is placed on nucleic acid delivery systems (NADS) based on polymers that respond to pathological or physiological changes in pH, redox state, enzyme levels, hypoxia, and reactive oxygen species levels. Additional discussion is focused on NADS suitable for applications that use external stimuli, such as light, ultrasound, and local hyperthermia.