Determination of Intimate Composition of Theranostic Polyplexes Based on (Co)Polymers of Poly(vinyl benzyl trimethylammonium chloride)

Novel hybrid nanoparticulate systems that exhibit potential to combine therapeutic, diagnostic, and sensing modalities in a single nanoparticle are investigated. They are composed of a homopolymer of poly(vinyl benzyl trimethylammonium chloride) (or its copolymer with poly[oligo(ethylene glycol) methacrylate]), DNA, and gold nanoparticles (AuNPs). Using the approach of classic dynamic and static light scattering, parameters such as molar mass, particle size, geometry and density, and intimate composition are determined, trying to establish what the theranostic polyplexes really carry. According to the analysis, the polyplex particles are composed of up to 154 DNA molecules and 1612 (co)polymer molecules at amino‐to‐phosphate groups ratio (N/P) of 0.5 and 1 DNA and up to 252 (co)polymer molecules at higher N/P ratios. The particle morphology is consistent with “hairy surface on a compact sphere” with density that is lower than the density of the familiar copolymer micelles. The introduction of AuNPs does not influence the density and structure of the carriers, which could be related to the low number fraction of polyplex particles carrying AuNPs. Additional data from transmission electron microscopy, electrophoretic light scattering, and analytical ultracentrifugation validate the morphology, structure, and molar mass of the theranostic nanoassemblies and confirm the conclusions derived from light scattering.