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 exp...