A biomimetic nano-platelet as an antidote for dual antiplatelet therapy-induced bleeding.

Dual Antiplatelet Therapy (DAPT) is a first-line clinical regimen for the prevention and treatment of arterial thrombosis, particularly in Acute Coronary Syndrome. However, its long-term application is compromised by a consequential risk of hemorrhage, which can be life-threatening and presents a major clinical dilemma in antithrombotic management. Inspired by the pharmacological mechanism of antiplatelet agents, we have engineered a biomimetic nano-platelet, termed Lys@MSN@CM (LMCM), for the efficient reversal of DAPT-induced bleeding. LMCM is architected from a megakaryocyte-derived membrane shell with high P2Y12 receptor expression, and a mesoporous silica core encapsulating lysine. This formulation enables simultaneous antagonism of P2Y12 receptor inhibitors (e.g., ticagrelor, clopidogrel) and cyclooxygenase-1 inhibitor (e.g., aspirin), thereby achieving synergistic reversal of DAPT. In vitro and in vivo assessments demonstrated that LMCM potently restored DAPT-impaired platelet aggregation and attenuated bleeding complications. This study pioneers a strategy for the synergistic management of DAPT-associated hemorrhagic events, presenting a promising platform to safeguard long-term DAPT administration.