Engineered Bio-Heterojunction with Robust ROS-Scavenging and Anti-Inflammation for Targeted Acute Pancreatitis Therapy

Abstract

Acute pancreatitis (AP) is one of the most severe mortal inflammatory diseases worldwide, which is characterized by the over-activation of reactive oxygen species (ROS)-induced inflammation and pancreatic enzymes (PEs). As the PEs induced by ROS exacerbate the progression of AP, therefore, scavenging ROS within PEs is a prerequisite for AP treatment. To address the daunting issue, the engineered bio-heterojunctions (bio-HJs) consisting of Mo2C-Au (MA), phospholipid, and protease inhibitors are devised. First, the decorated phospholipid and protease inhibitors facilitate the delivery of MA to the inflammatory pancreas as well as neutralization of PEs. Next, the MA exhibits outstanding antioxidant and ROS scavenging abilities, primarily benefiting from the increased empty orbitals on Mo attributed to electron transfer between the Mo2C and Au confirmed by theoretical calculation. The in vitro experiments demonstrate that the bio-HJs exhibit splendid biocompatibility, excellent trypsin neutralization, and efficient ROS elimination properties. More encouragingly, the in vivo studies further reveal that the bio-HJs prevent the infiltration of inflammatory cells and alleviate the severity of AP by suppressing the ROS-induced activation of the TLR4-ERK1/2 MAPK-MLCK inflammatory signaling pathway. As envisioned, the engineered bio-HJs represent a promising approach to the treatment and prevention of AP.