Gene therapy provides an alternative and effective method for treatment of genetic diseases and cancers that are refractory to conventional therapeutics. The success of gene therapy is largely dependent on the development of safe and effective gene delivery vectors for transporting genetic material from the blood stream to the cytoplasm or nucleus. Current gene vectors can be divided into viral and non-viral vectors. Although non-viral gene delivery carriers can offer some advantages, such as safety and facile fabrication, they do not possess the same high gene transfection efficiency as viral vectors due to a lack of functionality to overcome extra- and intracellular gene delivery obstacles. On the basis of these disadvantages, researchers are developing "smart" non-viral gene-delivery carriers in order to overcome the physiological barriers and realize efficient gene transfection. These "smart" stimuli-responsive carriers can undergo physical or chemical reactions in response to internal tumor-specific environments, such as pH conditions, redox potentials, enzymatic activations and thermal gradients, as well as external stimulations, such as ultrasound, light, magnetic fields, and electrical fields. Furthermore, "smart" carriers can also be triggered by dual or multiple combinations of different stimuli. In this review, we highlight the recent stimuli-sensitive polymeric nanocarriers for gene delivery, and we discuss the potential of combining multiple stimuli-responsive strategies for future gene therapy applications.
Keywords: Gene therapy; Nanocarriers; Non-viral vector; Polymer; Stimuli-responsive.