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A Single-Cell Atlas-Inspired Hitchhiking Therapeutic Strategy for Acute Pancreatitis by Restricting ROS in
Deyu Zhang1, Xinyue Wang1, Wanshun Li1
1Department of Gastroenterology, Shanghai Institute of Pancreatic Diseases, Changhai Hospital, National Key Laboratory of Immunity and Inflammation, Naval Medical University, Shanghai, 200433, China.
Advanced Materials (Deerfield Beach, Fla.)
|May 21, 2025
Summary
This study reveals neutrophil subtypes in acute pancreatitis (AP) and develops a nanoreactor to target and reprogram them. The therapy reduces inflammation by controlling neutrophil polarization and reactive oxygen species (ROS).
Area of Science:
- Immunology
- Nanomedicine
- Gastroenterology
Background:
- Neutrophils play a dual role in disease, contributing to inflammation or tissue repair through reprogramming.
- Understanding neutrophil subpopulations and polarization in acute pancreatitis (AP) is crucial for developing targeted therapies.
- N1 and N2 neutrophils represent distinct polarization states with differing roles in AP pathogenesis.
Purpose of the Study:
- To characterize neutrophil subpopulations and polarization pathways in acute pancreatitis (AP) using single-cell sequencing.
- To develop a novel nanoreactor for targeted modulation of neutrophil polarization in AP.
- To investigate the therapeutic potential of the nanoreactor in mitigating AP-associated inflammation.
Main Methods:
- Single-cell RNA sequencing was employed to identify distinct neutrophil subgroups and polarization pathways in AP.
- A hollow manganese dioxide (HMnO2)-based nanoreactor (Pyp@APHM) was engineered, conjugated with Ly-6G antibodies for neutrophil targeting.
- The nanoreactor was loaded with porphyrin, designed to release manganese ions and porphyrin ligands in the acidic AP microenvironment for in situ antioxidant synthesis.
Main Results:
- Single-cell sequencing identified distinct neutrophil subgroups and N1/N2 polarization pathways in AP.
- The Pyp@APHM nanoreactor effectively targeted AP sites by binding to neutrophils.
- The nanoreactor inhibited both N1 and N2 neutrophil polarization, reduced reactive oxygen species (ROS), and enhanced tissue oxygenation, thereby mitigating pancreatic inflammation.
Conclusions:
- This study provides a comprehensive single-cell atlas of neutrophils in AP.
- A novel 'hitchhiking' nanoreactor strategy effectively targets and modulates neutrophil polarization in AP.
- The developed nanoreactor offers a promising therapeutic approach for AP by controlling neutrophil responses and reducing oxidative stress.
