Self-Assembled Raspberry-Like Core/Satellite Nanoparticles for Anti-Inflammatory Protein Delivery. 
Functional proteins are very promising for protein therapeutics; however, effective delivery of therapeutic proteins remains challenging.  Herein, we developed novel core/satellite nanoparticles by tethering therapeutic proteins to the core/shell polymeric particle surface through cucurbit[8]uril (CB[8])-mediated host-guest interactions.  The effectiveness of the core/satellite nanoparticles as protein carrier was demonstrated through the intra-articular delivery of interleukin-1 receptor antagonist (IL-1Ra).  We showed that IL-1Ra can effectively self-assemble onto the surface of the polymeric nanoparticles and maintained good protein bioactivity by inhibiting IL-1-mediated signaling.  More importantly, in vivo results revealed that IL-1Ra-bounded core/satellite nanoparticles could significantly increase the retention time of IL-1Ra in the rat stifle joint compared to soluble IL-1Ra, which could greatly improve the efficacy of IL-1Ra.  These results indicate that the facile host-guest self-assembly can be exploited as an effective approach for realizing the therapeutic potential of proteins.