Facile approach for DNA encapsulation in functional polyion complex for triggered intracellular gene delivery:...

A facile route for DNA encapsulation in triggered intracellular degradable polymer microcapsules has been achieved via electrostatic interaction, using a polycation, that is, poly[(dimethylamino)ethyl methacrylate] end-capped with cholesterol moiety (Chol-PDMAEMA(30)), along with a polyanion named MePEG2000-block-poly(methacrylic acid) carring partial thiol groups (MePEG2000-b-PMAA(SH)). The encapsulation procedure involves three steps: (i) DNA was first complexed with the polycation (Chol-PDMAEMA(30)); (ii) the complex was then further set into interaction with the anion-containing MePEG2000-b-PMAA(SH); and (iii) the compound carrier was subsequently obtained by cross-linking the thiol groups of the MePEG2000-b-PMAA(SH) to form disulfide linkages. The interactions between every pair among calf thymus DNA, Chol-PDMAEMA(30), and MePEG2000-b-PMAA(SH) were studied by agarose gel retardation assay and ethidium bromide displacement assay. The results indicate that the prepared microcapsules may remain stable during systemic circulation, but degrade and release the carried DNA in a cellular reducing environment. Furthermore, the biophysical properties of the microcapsule have been investigated by zeta-potential, laser light scattering, and transmission electron microscopy (TEM) measurements.