Inflammation-responsive biomimetic nanoparticles for targeted acute pancreatitis therapy

Acute pancreatitis (AP) is a rapidly progressing and life-threatening inflammatory disease. Traditional medications have limitations such as a short half-life, low bioavailability, monofunctionality, and notable side effects, making it difficult to inhibit the progression of AP. We developed a biomimetic nanomedicine (MDU@Mn) that is responsive to and targets the pancreatic inflammatory microenvironment; the medicine consists of polydopamine nanoparticles coloaded with ulinastatin (U) and manganese ions and encapsulated with macrophage membranes. MDU@Mn evades immune system clearance, promotes nanoparticle enrichment at sites of inflammation, and exhibits improved bioavailability and a relatively long half-life. In addition, it specifically releases U and manganese ions in regions of the pancreas with low pH and high Reactive Oxygen Species (ROS) levels for image-guided therapy with fewer side effects. In vitro and in vivo studies demonstrated that MDU@Mn has excellent therapeutic and magnetic resonance imaging capabilities and can significantly reduce the levels of relevant indicators of inflammation in the pancreatic microenvironment (ROS, inflammatory cells, enzymes, etc.), preventing further expansion of inflammation. This study provides a new strategy for constructing a responsive multifunctional diagnostic and therapeutic platform for inflammatory microenvironments. • Synthesized biomimetic nanoparticles with the ability of immune escape and inflammation “homing”, actively targeting to the site of inflammation, prolonging the blood half-life, and improving the bioavailability. • Realize dual response of pH and ROS at the site of pancreatic inflammation, and specifically release urinastatin and manganese ions to improve therapeutic efficacy and reduce unnecessary side effects • Combining imaging and therapy for synergistic benefits to facilitate the early diagnosis of diseases, targeted drug distribution monitoring and treatment response assessment.