Magnetic Response Combined with Bioactive Ion Therapy: A RONS-Scavenging Theranostic Nanoplatform for Thrombolysis and Renal Ischemia–Reperfusion Injury

Abstract

Currently, the limited efficacy of antithrombotic treatments is attributed to the inadequacy of pure drugs and the low ability of drugs to target the thrombus site. More importantly, timely thrombolysis is essential to reduce the sequelae of cardiovascular disease, but ischemia−reperfusion injury (IRI) remains a major challenge that must be solved after blood flow recovery. Herein, a multifunctional therapeutic nanoparticle (NP) based on Fe 3 O 4 and strontium ions encapsulated in mesoporous polydopamine was successfully constructed and then loaded with TNK-tPA (FeM@Sr-TNK NPs). The NPs (59.9 min) significantly prolonged the half-life of thrombolytic drugs, which was 3.04 times that of TNK (19.7 min), and they had good biological safety. The NPs were shown to pass through vascular models with different inner diameters, curvatures, and stenosis under magnetic targeting and to enable accurate diagnosis of thrombi by photoacoustic imaging. NPs combined with the magnetic hyperthermia technique were used to accelerate thrombolysis and quickly open blocked blood vessels. Then, renal IRI-induced functional metabolic disorder and tissue damage were evidently attenuated by scavenging toxic reactive oxygen and nitrogen species and through the protective effects of bioactive ion therapy, including reduced apoptosis, increased angiogenesis, and inhibited fibrosis. In brief, we constructed a multifunctional nanoplatform for integrating a "diagnosis-therapy-protection" approach to achieve comprehensive management from thrombus to renal IRI, promoting the advancement of related technologies.

Collagen-Targeting Self-Assembled Nanoprobes for Multimodal Molecular Imaging and Quantification of Myocardial Fibrosis in a Rat Model of Myocardial Infarction

“…CNA35-GP@NPs (1 mL, 6 mg/mL) with DiI were injected into SD rats. The pharmacokinetics of the CNA35-GP@NPs in healthy rats were determined as described in a previous study . Briefly, blood was collected at 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12, and 24 h after injection.…”

“…The pharmacokinetics of the CNA35-GP@NPs in healthy rats were determined as described in a previous study. 42 Briefly, blood was collected at 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, 12, and 24 h after injection. Finally, all fluorescence imaging was performed using IVIS and all the pictures were analyzed using IndiGO2 software.…”

Progress on Physical Field‐Regulated Micro/Nanomotors for Cardiovascular and Cerebrovascular Disease Treatment

“…With the magnetic targeting, this nanoplatform can pass through vascular models with different inner diameters, tortuosity, and stenosis, which could efficiently dissolve the thrombus and unclog the blocked blood vessels by combining with the magnetic hyperthermia. [ 135 ]…”

Magnetic Nanoparticles Mediated Thrombolysis–A Review

“…However, concerns about the biosafety and biometabolism of MNPs have also been raised, particularly in the context of in vivo applications [ 102 ]. Ferrite nanoparticles, such as iron oxide nanoparticles, are among the most widely used MNPs for in vivo applications, including thrombolysis [ 85 ], [ 103 ]. These nanoparticles have been shown to exhibit low toxicity and high biocompatibility, and they can be metabolized and excreted through the liver and spleen [ 104 ], [ 105 ].…”