Thrombolytic Agents: Nanocarriers in Targeted Release

Abstract

A thrombus, known as a blood clot, may form within the vascular system of the body and impede blood flow. Thrombosis is the most common underlying pathology of cardiovascular diseases, contributing to high morbidity and mortality. However, the main thrombolytic drugs (urokinase, streptokinase, etc.) have shortcomings, including a short half-life, serious side effects and a lack of targeting, that limit their clinical application. The use of nano-drug delivery systems is expected to address these problems and a variety of approaches, including biological and physical responsive systems, have been explored. In this report, recent advances in the development of targeted nano-drug delivery systems are thoroughly reviewed.

Platelet Membrane Cloaked Nanotubes to Accelerate Thrombolysis by Thrombus Clot‐Targeting and Penetration

“…The half‐life of Uk is <20 min in the blood circulation, [ 30,34 ] and delivery systems, as the NT‐RGD‐Uk/Pm we developed here, may prolong its half‐life. To verify this, the Cy5‐labeled Uk loaded in NT‐RGD and NT‐RGD/Pm were injected into mice via the tail vein, and serum was taken to quantitatively measure the half‐life of Uk by fluorescence.…”

RGD peptide modified RBC membrane functionalized biomimetic nanoparticles for thrombolytic therapy

“…At present, thrombolytic targeting strategies mainly include the use of ultrasound or magnetic field as external stimulation conditions to guide the drug carrier to the thrombus site to play a role, or to stimulate the specific binding of drug carrier and thrombus components to achieve the purpose of treatment [ 32 , 33 ]. For example, Zhou et al constructed Fe3O4-based PLGA nanoparticles (NPs) carrying recombinant tissue plasminogen activator (rtPA) (Fe3O4–PLGA-rtPA/CS-cRGD), which further coated with cyclic arginine-glycine-aspartic peptide (cRGD) grafted chitosan (CS) [ 34 ].…”

Clot‐targeted magnetic hyperthermia permeabilizes blood clots to make them more susceptible to thrombolysis

“…This includes using the nanoparticles to specifically target release of tPA at the clot, thus reducing the risk of intracranial hemorrhage from systemic application of this drug 35 . Additionally, further development of the composition and size of the magnetic nanoparticle core could allow these clot‐targeted nanoparticles to be used as a contrast agent to facilitate delivery of the magnetic nanoparticles into occluded blood vessels 38 the imaging of blood clots, 39 or for magnetic filtration of labeled emboli to prevent these lodging in other brain regions or in the lungs, minimizing the secondary consequences of thrombolysis 40 . Last, we recently demonstrated citrate‐coated magnetic nanoparticles such as these are able to slow platelet activation, which could further prevent additional thrombi forming 41 .…”