Abstract

Nucleic acid therapeutics (NATs) are valuable tools in the modulation of gene expression in a highly specific manner. So far, NATs have been actively pursued in both pre-clinical and clinical studies to treat diseases such as cancer, infectious and inflammatory diseases. However, the clinical application of NATs remains a considerable challenge owing to their limited cellular uptake, low biological stability, off-target effect, and unfavorable pharmacokinetics. One concept to address these issues is to deliver NATs within stimuli-responsive liposomes, which release their contents of NATs upon encountering environmental changes such as temperature, pH, and ion strength. In this case, before reaching the targeted tissue/organ, NATs are protected from degradation by enzymes and immune system. Once at the area of interest, localized and targeted delivery can be achieved with minimal influence to other parts of the body. Here, we discuss the latest developments and existing challenges in this field. From the Clinical EditorNucleic acid therapeutics have been shown to enhance or eliminate specific gene expression in experimental research. Unfortunately, clinical applications have so far not been realized due to problems of easy degradation and possible toxicity. The use of nanosized carriers such as liposomes to deliver nucleic acids is one solution to overcome these problems. In this review article the authors describe and discuss the potentials of various trigger-responsive "smart" liposomes, with a view to help other researchers to design better liposomal nucleic acid delivery systems.

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