Monitoring phospholipase A₂ activity with Gd-encapsulated phospholipid liposomes.
To date, numerous analytical methods have been developed to monitor phospholipase A2 (PLA2) activity. However, many of these methods require the use of unnatural PLA2 substrates that may alter enzyme kinetics, and probes that cannot be extended to applications in more complex environments. It would be desirable to develop a versatile assay that monitors PLA2 activity based on interactions with natural phospholipids in complex biological samples. Here, we developed an activatable T1 magnetic resonance (MR) imaging contrast agent to monitor PLA2 activity. Specifically, the clinically approved gadolinium (Gd)-based MR contrast agent, gadoteridol, was encapsulated within nanometer-sized phospholipid liposomes. The encapsulated Gd exhibited a low T1-weighted signal, due to low membrane permeability. However, when the phospholipids within the liposomal membrane were hydrolyzed by PLA2, encapsulated Gd was released into bulk solution, resulting in a measureable change in the T1-relaxation time. These activatable MR contrast agents can potentially be used as nanosensors for monitoring of PLA2 activity in biological samples with minimal sample preparation.
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Zhiliang
Z
Cheng
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
Andrew
A
Tsourkas
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000031:analogs & derivatives / Q000737:chemistry; D000818:Animals; D001095:Arachidonic Acids / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D017815:Elapidae / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D063065:Organophosphonates / Q000737:chemistry; D010539:Permeability; D010714:Phosphatidylethanolamines / Q000737:chemistry; D054467:Phospholipases A2 / Q000302:isolation & purification*; D011092:Polyethylene Glycols / Q000737:chemistry
C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D001095:Arachidonic Acids; D003287:Contrast Media; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; D063065:Organophosphonates; D010714:Phosphatidylethanolamines; C104810:methyl arachidonylfluorophosphonate; C062402:gadoteridol; D015060:1,2-Dipalmitoylphosphatidylcholine; C081581:colfosceril palmitate; D011092:Polyethylene Glycols; D005682:Gadolinium; D054467:Phospholipases A2