Overall, by targeting the delivery of BTK inhibitors into autoreactive B cells, the BTEL NPs realized BAFFR- and BCR-signal pathway blocking simultaneously, inhibiting the survival and activation of autoreactive B cells and improving the bioavailability of BTK inhibitors, which may provide a promising strategy for the treatment of SLE. Here, TNFRSF13C is linked to systemic lupus erythematosus.