TEM images of highly-uniform PEG-b-PPA/DNA micelles with different shapes prepared by controlling self-assembly conditions.
Recently, there is an increasing body of evidence indicating that the shape of polymeric or metallic nanoparticles plays important roles in dictating their bio-functionalities, including cell internalization, biodistribution and tissue uptake after in vivo delivery. However, for gene delivery mediated by polymer/DNA nanoparticles, there has been no systematic study to understand the role of nanoparticle shape on the transfection efficiency and transport properties. This is primarily due to the lack of a suitable method to control the shape of DNA-containing nanoparticles.
Our lab has developed a technique to manipulate the shapes of polymer/DNA micelles without changing polymer composition. By varying self-assembly conditions, polymer/DNA micelles with distinctly different shapes can be prepared at high uniformity. The resulting micelles closely mimic the typical shapes (spherical, rod-like, and worm-like morphologies), sizes (20 to 80 nm in diameter, hundreds of nm in length for worm-like micelles), and physical features (flexible and hydrated surfaces) of viral particles. More importantly, we have demonstrated that these polymer/DNA micelles with different shapes can mediate significantly different cellular uptake efficiency and gene delivery efficiency after in vivo delivery, which suggests that particle shape plays a very important role in determining the gene delivery of polymer/DNA nanoparticles.