Title: Double-NetworkNanogel as a Nonviral Vector for DNADelivery
Abstract: 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.