Heterocyclic Molecules Tethered Branched Polymers with Innate Immune Stimulating Activity

We report herein an interesting finding that heterocyclic molecules tethered branched polymers exhibit innate immune stimulating activity. When we conjugated a series of five-, six-, or seven-membered heterocyclic molecules to branched polyethylenimine (bPEI), over 70% of them could induce the secretion of interferon-ss (IFN-ss) from murine dendritic and human leukemia monocytic (DC2.4 and THP-1) cells through activating the stimulator of interferon genes (STING) pathway. We further proved that this kind of innate stimulating activity was dependent on the macromolecular architecture as heterocyclic molecules tethered linear PEI (lPEI) or dendritic polyamidoamine (PAMAM) induced no or much less IFN-ss secretion. Furthermore, we prepared a series of polyL-lysine (PLL)-derivatives with different branches to tether with heterocyclic molecules and proved that this kind of bPEI-like structure was important in en hancing the binding affinity with STING proteins and for exhibiting innate stimulating activity.