Reducible Disulfide-Based Non-Viral Gene Delivery Systems

Abstract

The design and synthesis of safe efficient non-viral vectors for gene delivery has attracted significant attention in recent years due primarily to the severe side-effect profile reported with the use of their viral counterparts. Previous experiments have revealed that the strong interaction between the carriers and nucleic acid may well hinder the release of the gene from the complex in the cytosol adversely affecting transfection efficiency. However, incorporating reducible disulfide bonds within the delivery systems themselves which are then cleaved in the glutathione-rich intracellular environment may help in solving this puzzle. This review focuses on recent development of these reducible carriers. The biological rationale and approaches to the synthesis of reducible vectors are discussed in detail. The in vitro and in vivo evaluations of reducible carriers are also summarized and it is evident that they offer a promising approach in non-viral gene delivery system design.

Reducible HPMA-co-oligolysine copolymers for nucleic acid delivery

“…Multiple groups have reported that the incorporation of disulfide linkages does not affect polyplex stability in salt (Ouyang et al, 2009). However, unlike HPMA-AhxK 10 polyplexes, polyplexes formed with HPMA-AedpK 10 were not salt stable.…”

“…To meet these two seemingly opposing material requirements, polycations that undergo triggered intracellular degradation have been employed. The two most commonly used strategies employed in design of degradable polycations are acid-labile bonds, such as hydrazones and esters, and reducible disulfide linkages (Bauhuber et al, 2009; Ganta et al, 2008; Ouyang et al, 2009). The latter approach is particularly attractive because the disulfide bonds are stable in the oxidizing extracellular environment while the reducing environment of the cell cytoplasm triggers intracellular degradation.…”

Disulfide bond based polymeric drug carriers for cancer chemotherapy and relevant redox environments in mammals

“…The significance of disulfide in the areas of chemistry, biology, pharmacology, and pharmaceutics has been recognized for several years . Furthermore, many reviews focus on the therapeutic gene delivery systems containing disulfide bonds and the corresponding evaluation of therapeutic efficacy . Recently, advances have been made in the project of disulfide linkage‐employing DDS for triggered intracellular drug release.…”

Lipopolyplex for Therapeutic Gene Delivery and Its Application for the Treatment of Parkinson’s Disease

“…The ECM and intracellular cytosol are highly oxidizing and reducing, respectively. In the cytosol, glutathione (GSH) exists in both reduced (GSH) and oxidized (disulfide) states and its concentration is about 1000 times higher which leads to a high redox potential gradient between the intracellular and ECM (Ouyang et al, 2009 ). Therefore, disulfide bonds will be reduced in the cytosol leading to high gene delivery efficiency.…”