Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

Abstract

Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide. However, current drug therapeutics are compromised by narrow therapeutic windows, unsatisfactory thrombolysis effects, severe bleeding events, and high recurrence rates. In this study, we exploit a self-propelling nano-penetrator with high fuel loading and controllable motion features, which is molecularly co-assembled using a photothermal photosensitizer (DiR) and a photothermal-activable NO donor (BNN6). The precisely engineered nano-penetrator of the BNN6-DiR fuel pair shows distinct advantages in terms of NO productivity and autonomous motion under laser irradiation. In animal models of artery/vein thrombosis and acute ischemic stroke, the self‐fueled nano-penetrator enables self-navigated thrombus-homing accumulation, self-propelled clot deep penetration, fluorescence image-guided photothermal/mechanical thrombolysis, and NO-mediated prevention of thrombosis recurrence and acute ischemic stroke salvage. As expected, the molecularly self-fueled nano-penetrator displayed favorable therapeutic outcomes without bleeding risk compared to the clinically available thrombolytic drug. This study offers a facile, safe, and effective nonpharmaceutical modality towards the clinical treatment of thrombosis and ischemic stroke.

Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke

“…Forty-eight hours after intravenous administration, brains were collected and cut into 1.5 mm intervals, and then stained by using 0.25% TTC dye at 37 °C for 0.5 h. The white area represents the infarct region. , …”

“…Forty-eight hours after intravenous administration, brains were collected and cut into 1.5 mm intervals, and then stained by using 0.25% TTC dye at 37 °C for 0.5 h. The white area represents the infarct region. 70,71 Detection of ROS in the Ischemic Brain. The ischemic hemispheres of brains were collected 24 h after administration and cut into pieces, followed by trypsin treatment to obtain cells for ROS detection.…”

Light-driven micro/nanomotors in biomedical applications

“…For example, Zhang et al elaborately engineered a carrier-free self-assembled nanomotor (T-BD NAs) consisting of a photothermal photosensitizer and a photothermal activable NO donor. 188 The concentration of NO produced by NIR light irradiation of T-BD NAs depends on the concentration of BNN6 and the magnitude of the laser radiation power. More interestingly, NO generation from T-BD NAs demonstrated regular off-on variations along with the laser irradiation switch, suggesting a controllable NO generation feature of laser irradiation T-BD NAs.…”

Nanotechnology in Stroke: New Trails with Smaller Scales

“…Following laser exposure, nanoformulation generated heat that facilitated its penetration into the clot and also generated nitric oxide. In animal models of acute ischemic stroke, the nanoformulation demonstrated better thrombolysis than the nanoparticle formulation without the photoactivation feature, and the produced nitric oxide prevented the recurrence of the clot formation [ 144 ].…”