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Thrombolytic therapy is one of the most effective treatments for thrombus dissolution and recanalization of blocked vessels in thrombotic diseases. However, the application of the thrombolytic strategy has been limited due to unsatisfactory thrombolytic efficacy, relatively higher bleeding complications, and consequently restricted indications. Recombinant staphylokinase (r-SAK) is a third-generation thrombolytic agent produced by genetic engineering technology, which exhibits a better thrombolytic efficacy than urokinase and recombinant streptokinase. Inspired by the natural affinity of platelets in hemostasis and pathological thrombosis, we developed a platelet membrane (PM)-coated r-SAK (PM-r-SAK). Results from animal experiments and human in vitro studies showed that the PM-r-SAK had a thrombolytic efficacy equal to or better than its 4-fold dose of r-SAK. In a totally occluded rabbit femoral artery thrombosis model, the PM-r-SAK significantly shortened the initial recanalization time compared to the same dose and 4-fold dose of r-SAK. Regarding the recanalized vessels, the PM-r-SAK prolonged the time of reperfusion compared to the same dose and 4-fold dose of r-SAK, though the differences were not significant. An in vitro thrombolytic experiment demonstrated that the thrombolytic efficacy of PM-r-SAK could be inhibited by platelet-poor plasma from patients taking aspirin and ticagrelor. PM coating significantly improves the thrombolytic efficacy of r-SAK, which is related to the thrombus-targeting activity of the PM-r-SAK and can be inhibited by aspirin- and ticagrelor-treated plasma.

Although treatments for myocardial infarction have advanced significantly, the global mortality due to ischemia and subsequent reperfusion injury remains high. Here, a platelet (PLT) membrane nanocarrier (PL720) that encapsulates L-arginine and FTY720 to facilitate the cascade-targeted delivery of these substances to the myocardial injury site and enable the controlled release of L-arginine and FTY720 is developed. Such an innovative approach shows enhanced cardioprotection through multiple target strategies involved in ischemia-reperfusion injury and late reperfusion inflammation. During the ischemia-reperfusion phase, PL720 targets and accumulates in damaged coronary arteries. PL720 rapidly releases L-arginine, stimulating endothelial cells to produce NO, thereby dilating blood vessels and promoting blood flow recovery, while FTY720's sustained release exerts anti-apoptotic effects. During the late reperfusion inflammatory phase, PL720 is captured by circulating inflammatory monocytes and transported into a deeper ischemic myocardial lesion. PL720 promotes macrophage polarization and accelerates the inflammatory repair. Furthermore, the issue of bradycardia associated with the clinical use of FTY720 is innovatively relieved. Therefore, PL720 is a vascular injury and inflammation dual targeting strategy, exhibiting significant potential for multi-targeted therapy and clinical translation for cardiac injury., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Platelet (PLT) membrane biomimetic nanomaterials have become promising theranostic platforms due to their good biocompatibility and effectiveness. However, in order to achieve precise regulation of cell membrane components, novel controllable construction approaches need to be developed. Inspired by the interaction mechanism among platelet production, activation, and dynamic biomechanical signals in blood circulation, here a platelet nanobubbles (PNBs) with reassembled platelet membrane with ideal echogenicity was fabricated using an adjustable pressure-induced shear stress method. The results demonstrate that the high shear stress during PNBs fabrication led to the enrichment of platelet membrane lipid rafts and proteins, as well as their reassembly on the gas-liquid interface. More importantly, the conformation of platelet integrin α IIb β 3 was transformed into a shear stress-induced intermediate affinity state, which gives PNBs enhanced adhesion ability to the vascular endothelial injury. Taken together, these PNBs have great application potential in the specifically targeted ultrasound diagnosis of vascular endothelial injury.

In recent years, a wide variety of bioinspired colloidal particles with novel cell mimetic functions have been the subject of extensive research in materials science, chemistry, biology, physics, and engineering. However, most of the approaches are derived from natural cell membrane coatings, which are still too primitive compared with living cells. In this study, we have chosen gold nanoparticles (GNPs) to explore the bioactivity response of living platelets and nanoparticle loading efficiency under different ultrasonic intensity and frequency treatment conditions. The results show that GNPs with no surface modification could be easily loaded into intra-platelets by both incubation (30 min) and ultrasonic exposure (1 min) methods. The amount of GNP loading was (4.4 ± 0.9) × 10 -3 and (5.8 ± 2.4) × 10 -3 pg per platelet upon incubation and acoustic triggering (1 MHz, 0.25 W cm -2 ), respectively. Although the other US treatment intensities (0.75, 1.50 and 2.25 W cm -2 ) also promoted higher amounts of GNPs in the platelets, the higher US intensity might bring about partial damage of the platelet membrane. Compared with 1 MHz ultrasonic exposure, the change of the GNP loading amount was not significantly higher upon ultrasonic frequency treatment of 45, 80 or 100 kHz. Therefore, it has been found that an US intensity of 0.25 W cm -2 could facilitate the intra-platelet delivery efficacy of the GNPs without damaging the biological activity. Furthermore, two possible pathways of GNPs entering into platelets upon US treatment are presented: one is the endocytosis/open canalicular system (OCS), and the other is cell membrane permeability enhancement, which is proved by the SEM and TEM results. Finally, the GNP-loaded platelets have been demonstrated as useful probes for photoacoustic imaging (PAI) and dark-field microscopy (DFM)-based imaging, which might allow a wide range of potential applications in diagnostics and therapy of platelet-related diseases.

Inspired by the nature, the biomimetic nanomaterial design strategies have attracted great interest because the bioinspired nanoplatforms may enhance the functionality of current nanoparticles. Especially, the cell membrane-derived nanoparticles can more effectively navigate and interact with the complex biological microenvironment. In this study, we have explored a novel strategy to rapidly in situ biosynthesize gold nanoparticles (GNPs) in living platelets with the help of ultrasound energy. Firstly, under the ultrasound exposure, the biocompatible chloroauric acid salts (HAuCl 4 ) can be enhanced to permeate into the platelet cytoplasm. Then, by the assist of reducing agent (NaBH 4 and sodium citrate) and platelet enzyme, GNPs were fast in situ synthesized in intra-platelets. The biosynthesized GNPs had a size of about 5 nm and were uniformly distributed in the cytoplasm. Atomic absorption spectrometry (AAS) showed the synthesized amount of Au is (12.7 ± 2.4) × 10 -3  pg per one platelet. The GNPs in platelets can produce Raman enhancement effect and further be probed for both dark-field microscopy (DFM)-based imaging and computed tomography (CT) imaging. Moreover, the platelets were not activated and remained aggregation bioactivity when intra-platelet GNPs synthesis. Therefore, such mimicking GNPs-platelets with in situ GNPs components remain inherent platelet bioactivity will find potential theranostic implications with unique GNPs properties., (Copyright © 2018 Elsevier B.V. All rights reserved.)