Advances on non-invasive physically triggered nucleic acid delivery from nanocarriers.

Nucleic acids (NAs) have been considered as promising therapeutic agents for various types of diseases. However, their clinical applications still face many limitations due to their charge, high molecular weight, instability in biological environment and low levels of transfection. To overcome these drawbacks, therapeutic NAs should be carried in a stable nanocarrier, which can be viral or non-viral vectors, and released at specific target site. Various controllable gene release strategies are currently being evaluated with interesting results. Endogenous stimuli-responsive systems, for example pH-, redox reaction-, enzymatic-triggered approaches have been widely studied based on the physiological differences between pathological and normal tissues. Meanwhile, exogenous triggered release strategies require the use of externally non-invasive physical triggering signals such as light, heat, magnetic field and ultrasound. Compared to internal triggered strategies, external triggered gene release is time and site specifically controllable through active management of outside stimuli. The signal induces changes in the stability of the delivery system or some specific reactions which lead to endosomal escape and/or gene release. In the present review, the mechanisms and examples of exogenous triggered gene release approaches are detailed. Challenges and perspectives of such gene delivery systems are also discussed.