Platelet Membrane Cloaked Nanotubes to Accelerate Thrombolysis by Thrombus Clot‐Targeting and Penetration

Abstract Thrombotic diseases have a high rate of mortality and disability, and pose a serious threat to global public health. Currently, most thrombolytic drugs especially protein drugs have a short blood‐circulation time, resulting in low thrombolytic efficiency. Therefore, a platelet membrane (Pm) cloaked nanotube (NT‐RGD/Pm) biomimetic delivery system with enhanced thrombolytic efficiency is designed. Nanotubes (NT) with an excellent clot‐penetration properties are used to load a protein thrombolytic drug urokinase (Uk). Platelet‐targeting arginine glycine‐aspartic peptide (RGD) is grafted onto the surface of the nanotubes (NT‐RGD) prior to cloaking. Multiple particle tracking (MPT) technique and confocal laser scanning microscope (CLSM) analysis are applied and the results show that the nanotubes possess a strong penetration and diffusion capacity in thrombus clots. After the Pm cloaking on NT‐RGD/Uk, it shows a thrombus microenvironmental responsive release property and the half‐life of Uk is six times longer than that of free Uk. Most importantly, NT‐RGD‐Uk/Pm exhibits a 60% thrombolytic efficiency in the FeCl 3 ‐induced thrombosis mouse model, and it is able to significantly reduce the bleeding side effects of Uk. This Pm‐cloaked nanotube system is an effective and promising platform for the controlled and targeted delivery of drugs for the thrombus treatment.