Polyplexes of DNA and Poly(l‑lysine) Stabilized by Au Nanoparticles for Targeted Photothermal Therapy

DNA polyplexes are classic nanomaterials used in the field of gene delivery because of their controllable biodegradability and biocompatibility. However, nanofabrication of DNA polyplexes as an organic building block has rarely been investigated, probably because of their low chemical and physical stability under various reaction conditions. In this study, we present the synthesis of highly stable DNA-poly-l-lysine (PLL) polyplexes and their use as cores to synthesize uniform gold nanoshells for photothermal therapy. To stabilize the DNA-PLL polyplexes, we introduced gold nanoparticles (AuNPs) to the polyplex surface (poly@AuNPs) through electrostatic and coordinate interactions of AuNPs with PLL and DNA, which significantly enhances the chemical and physical stability of the polyplexes, while maintaining their enzymatic biodegradability. Importantly, poly@AuNPs are suitable organic templates for the synthesis of polyplex core@gold nanoshells (poly@AuNSs) that exhibit excellent photothermal properties, high photothermal stability, and outstanding targeting ability toward cancer cells. The photothermal application of FA-modified poly@AuNSs for the elimination of tumors was practically demonstrated using nude mice. This study is the first demonstration of poly@AuNPs as chemically and physically stable yet biodegradable cores for nanoshell formation and, consequently, biomedical therapy, which sheds light on their potential applications in bioimaging, contrast agents, and organic templates for the synthesis of other functional nanostructures.