Engineered P2Y₁₂-Overexpressing Cell-Membrane-Wrapped Nanoparticles for the Functional Reversal of Ticagrelor and Clopidogrel.

Abstract

Antiplatelet agents, particularly P2Y₁₂ receptor inhibitors, are critical medicines in the prevention and treatment of thrombotic diseases in the clinic. However, their long-term use introduces a significant risk of bleeding in patients with cardiovascular diseases. Whether the bleeding is caused by the drug itself or due to surgical procedures or trauma, the need to rapidly reverse the effects of antiplatelet agents in the circulation is essential; however, no such agents are currently available. To address this need, here we describe a strategy that uses cell-membrane-wrapped nanoparticles (CM-NPs) for the rapid reversal of P2Y₁₂ inhibitors. CM-NPs are fabricated with membranes derived from 293T cells genetically engineered to overexpress the P2Y₁₂ receptor. Our findings support the potential of CM-NPs as a strategy for managing bleeding complications associated with P2Y₁₂ receptor inhibitors, offering an approach to improve the safety in the use of these drugs in clinical settings.