A trehalose-based polycation that contains lanthanide-chelate domains has been examined as a theranostic vehicle for siRNA delivery. By chelating the polymers with gadolinium and terbium ions, the polymers offer magnetic resonance and luminescence-based observation properties. Lanthanide resonance energy transfer (LRET) studies were examined with the Tb3+-chelated polymers (LRET donor) to monitor polyplex association with the LRET acceptor tetramethylrhodamine (TMR)-labeled siRNA. The polyplex formulations were compared to structures that do not contain trehalose within the polymer backbone and it was found that the presence of trehalose appears to increase siRNA delivery and gene knockdown efficiency in cultured glioblastoma cells (U87) that stably express luciferase. This study thus provides a preliminary theranostic polymer design model for delivery and monitoring of siRNA delivery.