Microwell array guided assembly of lipoplex nanoparticles containing siRNA

Nucleic acid based therapeutics has been widely explored to treat genetic and acquired diseases. However, the clinical translation of nucleic acid based therapies has been challenged by low delivery efficiency, off-target effects, poor cellular uptake, and limited serum stability. Lipopoplex nanoparticles, as one of the major nanocarrier systems, have shown great potential in overcoming these challenges. Current techniques for lipoplex nanoparticle preparation rely on self-assembly at macroscale, which suffers from limited control over particle structure and composition due to local fluctuations in the concentration of the constituent materials. We have developed a discontinuous dewetting/imprinting method that guided the assembly of lipoplex nanoparticles containing siRNA in a microwell array, which achieved much better control on particle size and composition. The lipoplex nanoparticles prepared by the discontinuous dewetting/imprinting method showed unilamellar core-shell-like structure in contrast to the multilamellar onion-like structure generally observed in lipoplex nanoparticles prepared by the conventional bulk mixing method.