MicroRNA Delivery with Bioreducible Polyethylenimine as a Non-Viral Vector for Breast Cancer Gene Therapy

Polyethylenimines (PEIs) are outstanding macromolecules belonging to the polycations used in gene transfection. The transfection efficiency and cytotoxicity of PEIs increase with the increase in their molecular weight. To break up the correlation between transfection efficiency and cytotoxicity for non-viral gene delivery, disulfide cross-linked polyethylenimine (PEI-SS) has been widely employed as highly efficient gene vectors for DNA/siRNA delivery in numerous efforts. In this work, PEI-SS is described as a non-viral vector for miRNA delivery for the first time. PEI-SS is synthesized via cross-linking using disulfide bonds as the cross-linker from low molecular weight PEI. PEI-SS can efficiently bind anti-miR-155 to form the polyplex with nano-sized spherical structures in the size range of 10-100 nm. The polyplex is degraded by glutathione (GSH, a reducing agent) in cancer cells. Anti-miR-155 is then released to efficiently inhibit tumor growth.