| Title: | Lure-and-kill macrophage nanoparticles alleviate the severity of experimental acute pancreatitis |
| Author(s): | Zhang Q; Zhou J; Zhou J; Fang RH; Gao W; Zhang L; |
| Address: | "Department of Nanoengineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. Department of Nanoengineering, Chemical Engineering Program, Moores Cancer Center, University of California San Diego, La Jolla, CA, USA. zhang@ucsd.edu" |
| DOI: | 10.1038/s41467-021-24447-4 |
| ISSN/ISBN: | 2041-1723 (Electronic) 2041-1723 (Linking) |
| Abstract: | "Acute pancreatitis is a disease associated with suffering and high lethality. Although the disease mechanism is unclear, phospholipase A2 (PLA2) produced by pancreatic acinar cells is a known pathogenic trigger. Here, we show macrophage membrane-coated nanoparticles with a built-in 'lure and kill' mechanism (denoted 'MPhi-NP(L&K)') for the treatment of acute pancreatitis. MPhi-NP(L&K) are made with polymeric cores wrapped with natural macrophage membrane doped with melittin and MJ-33. The membrane incorporated melittin and MJ-33 function as a PLA2 attractant and a PLA2 inhibitor, respectively. These molecules, together with membrane lipids, work synergistically to lure and kill PLA2 enzymes. These nanoparticles can neutralize PLA2 activity in the sera of mice and human patients with acute pancreatitis in a dose-dependent manner and suppress PLA2-induced inflammatory response accordingly. In mouse models of both mild and severe acute pancreatitis, MPhi-NP(L&K) confer effective protection against disease-associated inflammation, tissue damage and lethality. Overall, this biomimetic nanotherapeutic strategy offers an anti-PLA2 treatment option that might be applicable to a wide range of PLA2-mediated inflammatory disorders" |
| Keywords: | "Acute Disease/*therapy Animals Cytokines Disease Models, Animal Female Humans Inflammation *Macrophages Melitten Mice Nanoparticles/*therapeutic use Pancreatitis/*therapy Phospholipases A2/blood THP-1 Cells;" |
| Notes: | "MedlineZhang, Qiangzhe Zhou, Julia Zhou, Jiarong Fang, Ronnie H Gao, Weiwei Zhang, Liangfang eng Research Support, U.S. Gov't, Non-P.H.S. England 2021/07/08 Nat Commun. 2021 Jul 6; 12(1):4136. doi: 10.1038/s41467-021-24447-4" |
