| Title: | A Biomimetic Nanoparticle to 'Lure and Kill' Phospholipase A2 |
| Author(s): | Zhang Q; Fang RH; Gao W; Zhang L; |
| Address: | "Department of NanoEngineering, Chemical Engineering Program, and Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA" |
| ISSN/ISBN: | 1521-3773 (Electronic) 1433-7851 (Linking) |
| Abstract: | "Inhibition of phospholipase A2 (PLA2) has long been considered for treating various diseases associated with an elevated PLA2 activity. However, safe and effective PLA2 inhibitors remain unavailable. Herein, we report a biomimetic nanoparticle design that enables a 'lure and kill' mechanism designed for PLA2 inhibition (denoted 'L&K-NP'). The L&K-NPs are made of polymeric cores wrapped with modified red blood cell membrane with two inserted key components: melittin and oleyloxyethyl phosphorylcholine (OOPC). Melittin acts as a PLA2 attractant that works together with the membrane lipids to 'lure' in-coming PLA2 for attack. Meanwhile, OOPC acts as inhibitor that 'kills' PLA2 upon enzymatic attack. Both compounds are integrated into the L&K-NP structure, which voids toxicity associated with free molecules. In the study, L&K-NPs effectively inhibit PLA2-induced hemolysis. In mice administered with a lethal dose of venomous PLA2, L&K-NPs also inhibit hemolysis and confer a significant survival benefit. Furthermore, L&K-NPs show no obvious toxicity in mice. and the design provides a platform technology for a safe and effective anti-PLA2 approach" |
| Keywords: | "Animals Biomimetic Materials/chemistry/*pharmacology/toxicity Erythrocyte Membrane/chemistry Hemolysis/drug effects Human Umbilical Vein Endothelial Cells Humans Male Melitten/chemistry/*pharmacology/toxicity Mice, Inbred ICR Nanoparticles/*chemistry/toxi;" |
| Notes: | "MedlineZhang, Qiangzhe Fang, Ronnie H Gao, Weiwei Zhang, Liangfang eng Research Support, U.S. Gov't, Non-P.H.S. Germany 2020/03/24 Angew Chem Int Ed Engl. 2020 Jun 22; 59(26):10461-10465. doi: 10.1002/anie.202002782. Epub 2020 Apr 15" |
