Cyclic RGD functionalized PLGA nanoparticles loaded with noncovalent complex of indocyanine green with urokinase for synergistic thrombolysis

Abstract

Thrombotic diseases have the characteristics of long latency period, rapid onset, and high mortality rate, which seriously threaten people’s life and health. The aim of this research is to fabricate a novel indocyanine green complex of urokinase (ICG@uPA) and employ the amphiphilic PEG-PLGA polymer to deliver the complex as an enzyme-phototherapeutic synergistic thrombolysis platform. The noncovalent indocyanine green (ICG) complex of urokinase (ICG@uPA) was prepared via supramolecular self-assembly and then encapsulated into cRGD decorated polymeric nanoparticles (cRGD-ICG-uPA NPs) by double-emulsion solvent evaporation method. Then the nanoparticles (NPs) were characterized in terms of particle size, optical properties, in vitro release, etc. The targeting and thrombolytic effect of the nanoparticles were studied both in vitro and in vivo. ICG@uPA and cRGD-ICG-uPA NPs displayed significantly higher photostability and laser energy conversion efficiency than free ICG. Concomitantly, the NPs exhibited selective binding affinity to the activated platelets and specific accumulation in the mouse mesenteric vessel thrombus. Significant thrombolysis was achieved in vivo by photo-assisted synergistic therapy with reduced dose and systemic bleeding risk of uPA. Our results prove that the functional PLGA nanoparticle loaded with the ICG@uPA offers a novel option for effective and safe thrombolytic treatment.

Advances in Nano-Functional Materials in Targeted Thrombolytic Drug Delivery

“…After 808 nm laser irradiation, the thrombus treated with nanoparticles decreased to 14% of its original size. The results show that this collaborative thrombolytic strategy can significantly improve the accuracy and efficiency of thrombolytic therapy, and its metabolic clearance characteristics bring more possibilities for clinical application [96].…”

The Recent Applications of PLGA-Based Nanostructures for Ischemic Stroke

“…According to the results of the in vitro thrombolysis experiments, the thrombolysis rate was 72% in the cRGD-ICG-uPA NPs group and 60% in the free uPA group. The average time for hemostasis in the cRGD-ICG-uPA NPs group was around 200 s, while in the free uPA group it was around 600 s [ 66 ].…”