Since its discovery in the late 1990, small interfering RNA (siRNA) have quickly crept into the biopharmaceutical
research as a new and powerful tool for the treatment of different human diseases based on altered
gene-expression. Despite promising data from many pre-clinical studies, concrete hurdles still need to be overcome
to bring therapeutic siRNAs in clinic. The design of stimuli-sensitive nanopreparations for gene therapy is a lively
area of the current research. Compared to conventional systems for siRNA delivery, this type of platform can respond
to local stimuli that are characteristics of the pathological area of interest, allowing the release of nucleic acids
at the desired site. Acidic pH, de-regulated levels of enzymes, altered redox potential and magnetic field are examples
of stimuli exploit to design stimuli-sensitive nanoparticles. In this review, we discuss on recent stimulisensitive
strategies for siRNA delivery and we highlight on the potential of combining multiple stimuli-sensitive strategies in the same
nano-platform for a better therapeutic outcome.
Keywords: Stimuli-sensitivity, nanoparticles, siRNA delivery, PEGylated nano-systems, combined therapy, multifunctional nanoparticles.
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