High-loading Gα13-binding EXE peptide nanoparticles prevent thrombosis and protect mice from cardiac ischemia/reperfusion injury.

Science Translational Medicine
Aiming PangXiaoping Du

Abstract

Inefficient delivery is a major obstacle to the development of peptide-based drugs targeting the intracellular compartment. We recently showed that selectively inhibiting integrin outside-in signaling using a peptide (mP6) derived from the Gα13-binding ExE motif within the integrin β3 cytoplasmic domain had antithrombotic effects. Here, we engineered lipid-stabilized, high-loading peptide nanoparticles (HLPN), in which a redesigned ExE peptide (M3mP6) constituted up to 70% of the total nanoparticle molarity, allowing efficient in vivo delivery. We observed that M3mP6 HLPN inhibited occlusive thrombosis more potently than a clopidogrel/aspirin combination without adverse effects on hemostasis in rodents. Furthermore, M3mP6 HLPN synergized with P2Y12 receptor inhibitors or the clopidogrel/aspirin combination in preventing thrombosis, without exacerbating hemorrhage. M3mP6 HLPN also inhibited intravascular coagulation more potently than the P2Y12 inhibitor cangrelor. Postischemia injection of M3mP6 HLPN protected the heart from myocardial ischemia-reperfusion injury in a mouse model. This study demonstrates an efficient in vivo peptide delivery strategy for a therapeutic that not only efficaciously prevented thrombosis with minima...Continue Reading

References

Nov 2, 2002·Nature Medicine·Zaverio M Ruggeri
Sep 8, 2005·The Journal of Biological Chemistry·Jasna A MarjanovicXiaoping Du
Nov 10, 2009·Behavior Research Methods·Franz FaulAlbert-Georg Lang
Nov 17, 2009·The New England Journal of Medicine·Deepak L BhattUNKNOWN CHAMPION PLATFORM Investigators
Mar 24, 2010·Nature Reviews. Molecular Cell Biology·Sanford J ShattilMark H Ginsberg
Nov 13, 2010·Arteriosclerosis, Thrombosis, and Vascular Biology·Zhenyu LiXiaoping Du
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·B S Coller
Aug 9, 2011·Blood·Kelly A O'BrienXiaoping Du
Mar 12, 2013·The New England Journal of Medicine·Deepak L BhattUNKNOWN CHAMPION PHOENIX Investigators
Apr 13, 2013·Circulation Research·Kamila BledzkaEdward F Plow
May 24, 2013·The New England Journal of Medicine·Peter Libby
Apr 22, 2014·Journal of Visualized Experiments : JoVE·Zhaobin XuNoah Weisleder
May 17, 2014·Journal of Thrombosis and Thrombolysis·Gjin NdrepepaAdnan Kastrati
May 30, 2014·Blood·Lacramioara IvanciuRodney M Camire
Sep 27, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Brian EstevezXiaoping Du
Dec 3, 2014·Drug Discovery Today·Keld Fosgerau, Torsten Hoffmann
Apr 4, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Pat MetharomRobert K Andrews
Jul 15, 2015·The Journal of Experimental Medicine·Tadayuki YagoRodger P McEver
Jan 27, 2017·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee
Feb 24, 2017·Physiology·Brian Estevez, Xiaoping Du

❮ Previous
Next ❯

Citations

Mar 12, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Zheng XuXiaoping Du
May 29, 2021·Nature Communications·Ni ChengXiaoping Du

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cardiac Regeneration

Cardiac regeneration enables the repair of irreversibly damaged heart tissue using cutting-edge science, including stem cell and cell-free therapy. Discover the latest research on cardiac regeneration here.