Magnetic Response
Combined with Bioactive Ion Therapy:
A RONS-Scavenging Theranostic Nanoplatform for Thrombolysis and Renal
Ischemia–Reperfusion Injury
posted on 2023-03-17, 17:36authored byLian Xu, Ying Luo, Qianying Du, Wenli Zhang, Liu Hu, Ni Fang, Junrui Wang, Jia Liu, Jun Zhou, Yixin Zhong, Yun Liu, Haitao Ran, Dajing Guo, Jie Xu
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 Fe3O4 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.