Recent Advances in Tissue plasminogen activator-based nanothrombolysis for ischemic stroke

Abstract

Stroke is an acute cerebrovascular disorder caused by sudden decrease or interruption of blood flow in brain arteries. Deficiency of timely and effective reperfusion of ischemic brain tissue can lead to irreversible brain injury and neurological dysfunction. Currently, recombinant tissue plasminogen activator (rt-PA) is the only appropriate thrombolytic agent which is approved by FDA for patients with acute ischemic stoke. However, due to the limitation of very narrow therapeutic time window and severe intracranial hemorrhagic complication, the outcome of stroke treatment mediated by rt-PA still remains unsatisfactory. Therefore, it is urgent to find new alternative drugs or develop novel drug delivery system to achieve better outcomes. In recent years, with the rapid development of nanotechonology, nanomaterials as a drug delivery system can provide new strategies and methods to carry t-PA specifically to the occlusion site and provide advanced treatment for stroke. In this review, we briefly introduced the physiopathologic mechanisms of thrombolysis and focused on the comparison of the t-PA mediated thrombolysis and t-PA conjugated nanomaterial mediated thrombolysis.

A new classification method of nanotechnology for design integration in biomaterials

“…Surface modification with NPs still maintains the anticoagulation function and can selectively regulate cell behavior, which may have promising application in the field of intravascular stents. Tissue plasminogen activator has also been widely studied as a thrombolytic agent, using different materials such as polymers, micelles and microbubbles to achieve drug targeting, protection and release to the lesion location [51]. With the aim of sustained neovascularization, Chiappini et al delivered the VEGF-165 gene into cells by using biodegradable silicon nanoneedles [52].…”

Therapeutic Nanomaterials for Neurological Diseases and Cancer Therapy

“…However, there are no more effective treatments in clinical practice, except for tissue plasminogen activator-(tPA-) mediated thrombolytic or mechanical thrombectomy within the prescribed time [52,53]. Currently, nanomaterials are considered to have great potential in the field of stroke treatment [54,55]. Three research directions attract the most attention: (i) construction of safer and more efficient tPAcoated nanomaterials, (ii) antioxidants delivered through nanomaterials to reduce reperfusion injury, and (iii) generation of neuroprotective nanoscale exosomes.…”

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“…Molecular diagnostics based on nanotechnology, such as the development of biomarkers, can accurately and quickly detect the cancers 4 . Nanotechnology treatments, such as the development of nanoscale drug delivery, can ensure precise cancerous tissue targeting with minimal side effects 5 , 6 . Due to its biological nature, nanomaterials can easily cross cell barriers 7 .…”