Utilizing neutrophils (NEs) to target and deliver nanodrugs to inflammation sites has received considerable attention. NEs are involved in the formation and development of thrombosis by transforming into neutrophil extracellular traps (NETs); this indicates that NEs may be a natural thrombolytic drug delivery carrier. However, NEs lack an effective power system to overcome blood flow resistance and enhance targeting efficiency. Herein, we report the application of a urease catalysis micromotor powered NEs nanodrug delivery system to promote thrombolysis and suppress rethrombosis. The urease micromotor powered Janus NEs (UM-NEs) were prepared by immobilizing the enzyme asymmetrically onto the surface of natural NEs and then loading urokinase (UK) coupled silver (Ag) nanoparticles (Ag-UK) to obtain the UM-NEs (Ag-UK) system. Urease catalytic endogenous urea is used to generate thrust by producing ammonia and carbon dioxide, which propels NEs actively targeting the thrombus. The UM-NEs (Ag-UK) can be activated by enriched inflammatory cytokines to release NETs at the thrombosis site, resulting in a concomitant release of Ag-UK. Ag-UK induces thrombolysis to restore vascular recanalization. This urease micromotor-driven NEs drug delivery system can significantly reduce the hemorrhagic side effects, promote thrombolysis, and inhibit rethrombosis with high bioavailability and biosafety, which can be used for the treatment of thrombotic diseases.

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D39 inhibited tissue factor expression and thrombus formation by modulating the Akt/GSK3β and NF-κB signalling pathways through NMMHC IIA. We identified a new natural product that targeted NMMHC IIA, as a potential treatment for thrombotic disorders and other vasculopathies.

The development of tumor-associated, stimuli-driven, turn-on near-infrared (NIR) fluorophores requires urgent attention because of their potential in selective and precise tumor diagnosis. Herein, we describe a NIR fluorescent probe (CyA-cRGD) comprised of a fluorescence reporting unit (a cyanine dye) linked with a GSH-responsive unit (nitroazo aryl ether group) and a tumor-targeting unit (cRGD). The NIR fluorescence of CyA-cRGD with sensitive and selective response to GSH can act as a direct off-on signal reporter for GSH monitoring. Notably, CyA-cRGD possesses improved biocompatibility compared with CyA, which is highly desirable for in vivo fluorescence tracking of cancer. Confocal fluorescence imaging confirmed the tumor-targeting capability and GSH detection ability of CyA-cRGD in tumor cells, normal cells, and coincubated tumor /normal cells and in the three-dimensional multicellular tumor spheroid. Furthermore, it was validated that CyA-cRGD could detect tumor precisely in GSH and integrin αβ high-expressed tumor-bearing mouse models. Importantly, it was confirmed that CyA-cRGD possessed high efficiency for early-stage tumor imaging in mouse models with tumor cells implanted within 72 h. This method provided significant advances toward more in-depth understanding and exploration of tumor imaging, which may potentially be applied for clinical early tumor diagnosis.

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