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.
Innovative Drug Research Centre and School of Pharmaceutical Sciences, Chongqing University , Chongqing 401331, China.
Tingting
T
Wang
Innovative Drug Research Centre and School of Pharmaceutical Sciences, Chongqing University , Chongqing 401331, China.
Yaqin
Y
Tang
Innovative Drug Research Centre and School of Pharmaceutical Sciences, Chongqing University , Chongqing 401331, China.
Xiao
X
He
Innovative Drug Research Centre and School of Pharmaceutical Sciences, Chongqing University , Chongqing 401331, China.
Ju
J
Yan
Innovative Drug Research Centre and School of Pharmaceutical Sciences, Chongqing University , Chongqing 401331, China.
Chenhui
C
Wang
Innovative Drug Research Centre and School of Pharmaceutical Sciences, Chongqing University , Chongqing 401331, China.
Xuli
http://orcid.org/0000-0003-0476-9346
X
Feng
D000818:Animals; D000893:Anti-Inflammatory Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053758:Nanoparticles; D011108:Polymers; D051381:Rats
D000893:Anti-Inflammatory Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D011108:Polymers
IL-1Ra; core/satellite structure; host−guest interaction; protein delivery; self-assembly