JAM-2 siRNA intracellular delivery and real-time imaging by proton-sponge coated quantum dots

In this study, proton-sponge coated quantum dots were prepared by using amphipol PMAL, grafted with polyethylenimine (PEI) as an encapsulation polymer. The QD-PMAL-PEI nanoparticles showed low cytotoxicity and superior gene silencing efficiency in serum-containing medium against junctional adhesion molecule-2 (JAM-2), which is over-expressed in glioma cells. Confocal microscopic analysis showed efficient siRNA intracellular release. In particular, QD-mediated JAM-2 knockdown was reported for the first time to facilitate inhibition of glioma cell migration. Furthermore, the Notch pathway served as the target for the JAM-2 gene function, confirmed by downregulation of its downstream genes HES1 and HES5. The unique proton-sponge coated QDs can serve as multifunctional siRNA carriers for efficient gene silencing and real-time intracellular imaging, and provide a base for design of novel efficient siRNA delivery carriers with high biocompatibility.