Stimuli-responsive HA-PEI nanoparticles encapsulating endostatin plasmid for stem cell gene therapy

In this study, an environmentally-sensitive hyaluronic acid (HA)-polyethylenimine (PEI) copolymer with disulfide linkage is synthesized, characterized and examined as a potential non-viral gene vector. From the results, a redox- and pH-sensitive gene delivery nanocarrier has been successfully synthesized via the analysis of 1H NMR and FT-IR. The positive HA-ss-PEI conjugate complexed with negatively charged plasmid DNA can be achieved via electrostatic attraction to form a stable spherical nanoparticle of 100 to 200 nm in diameter. N/P = 2 possesses the optimal condition for releasing encapsulated plasmid when triggered by stimuli such as redox reaction and pH change. The HA-ss-PEI/pEndo nanocarrier can transfect human mesenchymal stem cells to produce endostatin protein and these hMSCs are capable of differentiating into functional chondrocytes after 7 days chondrogenic induction. The nano-encapsulation of genetic anti-angiogenesis factor combined with the chondrogenic induction of hMSCs may offer an alternative choice and potentially effective administration strategy for arthritis.