Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41467-021-24447-4
Keywords
-
Categories
Funding
- National Science Foundation [DMR-1904702]
- Defense Threat Reduction Agency Joint Science and Technology Office for Chemical and Biological Defense [HDTRA1-18-1-0014]
Ask authors/readers for more resources
The study presents a novel nanotherapeutic approach for treating acute pancreatitis by using macrophage membrane-coated nanoparticles, which effectively reduce inflammation and tissue damage associated with the disease.
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 'M Phi -NP(L&K)') for the treatment of acute pancreatitis. M Phi -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, M Phi -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. Phospholipase A2 (PLA2) inhibitors have been shown to be able to treat acute pancreatitis, but are toxic with systemic application. Here the authors design a nanoparticle with macrophage membrane components to carry PLA2 inhibitor to macrophages and treat pancreatitis in mice, with no evidence of toxicity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available