Intrinsic Radical Species Scavenging Activities of Tea Polyphenols Nanoparticles Block Pyroptosis in Endotoxin-Induced Sepsis

Sepsis, a life-threating illness caused by deregulated host immune responses to infections, is characterized by overproduction of multiple reactive oxygen and nitrogen species (RONS) and excessive pyroptosis, leading to high mortality. However, there is still no approved specific molecular therapy to treat sepsis. Here we reported drug-free tea polyphenols nanoparticles (TPNs) with intrinsic broad-spectrum RONS scavenging and pyroptosis-blocking activities to treat endotoxin (LPS)-induced sepsis in mice. The RONS scavenging activities originated from the polyphenols-derived structure, while the pyroptosis blockage was achieved by inhibiting gasdermin D (GSDMD) mediating the pore formation and membrane rupture, showing multifunctionalities for sepsis therapy. Notably, TPNs suppress GSDMD by inhibiting the oligomerization of GSDMD rather than the cleavage of GSDMD, thus displaying high pyroptosis-inhibition efficiency. As a result, TPNs showed an excellent therapeutic efficacy in sepsis mice model, as evidenced by survival rate improvement, hypothermia amelioration, and the organ damage protection. Collectively, TPNs present biocompatible candidates for the treatment of sepsis.

Automated summary

In this study, drug-free tea polyphenols nanoparticles (TPNs) were developed as a potential therapy for sepsis. TPNs exhibited both broad-spectrum reactive oxygen and nitrogen species (RONS) scavenging activity and pyroptosis-blocking activity, making them effective in treating endotoxin-induced sepsis in mice. The mechanism of action involved inhibiting gasdermin D (GSDMD) to prevent membrane rupture and pore formation. The TPNs showed excellent therapeutic efficacy, improving survival rates and protecting against organ damage.