Due to the mortality associated with thrombosis and its
high recurrence
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, poor ability to penetrate clots, rapid half-life, lack
of vascular restoration mechanisms, and risk of thrombus recurrence
that is comparable to that of traditional pharmacological thrombolysis
agents. Therefore, it is vital to develop an alternative technique
that can overcome the aforementioned limitations. To this end, a cotton-ball-shaped
platelet (PLT)-mimetic self-assembly framework engineered with a phototherapeutic
poly(3,4-ethylenedioxythiophene) (PEDOT) platform has been developed.
This platform is capable of delivering a synthetic peptide derived
from hirudin P6 (P6) to thrombus lesions, forming P6@PEDOT@PLT nanomotors
for noninvasive site-specific thrombolysis, effective anticoagulation,
and vascular restoration. Regulated by P-selectin mediation, the P6@PEDOT@PLT
nanomotors target the thrombus site and subsequently rupture under
near-infrared (NIR) irradiation, achieving desirable sequential drug
delivery. Furthermore, the movement ability of the P6@PEDOT@PLT nanomotors
under NIR irradiation enables effective penetration deep into thrombus
lesions, enhancing bioavailability. Biodistribution analyses have
shown that the administered P6@PEDOT@PLT nanomotors exhibit extended
circulation time and metabolic capabilities. In addition, the photothermal
therapy/photoelectric therapy combination can significantly augment
the effectiveness (ca. 72%) of thrombolysis. Consequently, the precisely
delivered drug and the resultant phototherapeutic-driven heat-shock
protein, immunomodulatory, anti-inflammatory, and inhibitory plasminogen
activator inhibitor-1 (PAI-1) activities can restore vessels and effectively
prevent rethrombosis. The described biomimetic P6@PEDOT@PLT nanomotors
represent a promising option for improving the efficacy of antithrombotic
therapy in thrombus-related illnesses.