Double-Network Nanogel as a Nonviral Vector for DNA Delivery

A double-network nanogel, composed of a silane-cross-linked polyethylenimine (PEI) network (i.e., PEI-S) and a pH-responsive poly(2-(hexamethyleneimino) ethyl methacrylate) (PC7A) polymer, was developed for efficient DNA transfection. The chemical cross-linking and hydrophobic interactions in the two networks led to improved stability outside the cell and also pH-triggered intracellular release of DNA. The nanogel with an optimal PEI-S and PC7A weight ratio of 1.3:1 exhibited significantly higher transfection efficiency than Lipofectamine 2000 in multiple cell lines. The nanogel also possessed a small size with a hydrodynamic diameter of 55 nm, low cytotoxicity, and superior stability in serum-containing media. Moreover, besides the PEI-based gene delivery system, we have also demonstrated that addition of the PC7A polymer to several types of cationic polymers commonly used for gene delivery also led to significant transfection enhancement of the resulting nanoparticles, suggesting that the PC7A polymer may be a universal additive that can benefit versatile cationic polymer-based gene delivery systems.