Biomimetic Platelet Nanomotors for Site-Specific Thrombolysis and Ischemic Injury Alleviation

•  Due to the mortality associated with thrombosis and its highrecurrence rate, there is a need to investigate antithrombotic approaches.Noninvasive site-specific thrombolysis is a current approach being used; however,its usage is characterized by the following limitations: low targeting efficiency, poorability to penetrate clots, rapid half-life, lack of vascular restoration mechanisms,and risk of thrombus recurrence that is comparable to that of traditionalpharmacological thrombolysis agents. Therefore, it is vital to develop an alternativetechnique that can overcome the aforementioned limitations. To this end, a cottonball-shaped platelet (PLT)-mimetic self-assembly framework engineered with aphototherapeutic poly(3,4-ethylenedioxythiophene) (PEDOT) platform has beendeveloped. This platform is capable of delivering a synthetic peptide derived fromhirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors fornoninvasive site-specific thrombolysis, effective anticoagulation, and vascularrestoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT nanomotors target the thrombus site and subsequentlyrupture under near-infrared (NIR) irradiation, achieving desirable sequential drug delivery. Furthermore, the movement ability ofthe P6@PEDOT@PLT nanomotors under NIR irradiation enables effective penetration deep into thrombus lesions, enhancingbioavailability. Biodistribution analyses have shown that the administered P6@PEDOT@PLT nanomotors exhibit extendedcirculation time and metabolic capabilities. In addition, the photothermal therapy/photoelectric therapy combination cansignificantly augment the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely delivered drug and the resultantphototherapeutic-driven heat-shock protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen activator inhibitor1 (PAI-1) activities can restore vessels and effectively prevent rethrombosis. The described biomimetic P6@PEDOT@PLTnanomotors represent a promising option for improving the efficacy of antithrombotic therapy in thrombus-related illnesses.

Ämnesord

TEKNIK OCH TEKNOLOGIER  -- Medicinteknik -- Medicinsk material- och protesteknik (hsv//swe)

ENGINEERING AND TECHNOLOGY  -- Medical Engineering -- Medical Materials (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomaterialvetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomaterials Science (hsv//eng)

Nyckelord

hirudin peptide

photothermal/photoelectric thrombolysis

vascular restoration

platelet nanomotor

drug delivery

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