Delivery of Nucleic Acids via Disulfide-Based Carrier Systems

Nucleic acids are not only expected to assume a pivotal position as “drugs” in the treatment of genetic and acquired diseases, but could also act as molecular cues to control the microenvironment during tissue regeneration. Despite this promise, the efficient delivery of nucleic acids to their side of action is still the major hurdle. One among many prerequisites for a successful carrier system for nucleic acids is high stability in the extracellular environment, accompanied by an efficient release of the cargo in the intracellular compartment. A promising strategy to create such an interactive delivery system is to exploit the redox gradient between the extra‐ and intracellular compartments. In this review, emphasis is placed on the biological rationale for the synthesis of redox sensitive, disulfide‐based carrier systems, as well as the extra‐ and intracellular processing of macromolecules containing disulfide bonds. Moreover, the basic synthetic approaches for introducing disulfide bonds into carrier molecules, together with examples that demonstrate the benefit of disulfides at the individual stages of nucleic acid delivery, will be presented. Materials containing disulfide bonds are very promising for the delivery of nucleic acids into cells, because they exploit the redox gradient between the extra‐ and intracellular compartment. This review gives an overview of the biological rationale for the synthesis of redox‐sensitive, disulfide‐based carrier systems. In particular, the basic synthesis approaches for introducing disulfide bonds into carrier molecules are presented.