Near‐Infrared Triggered Release of uPA from Nanospheres for Localized Hyperthermia‐Enhanced Thrombolysis

Abstract

Currently, most thrombolytic agents are limited by short circulation time and excessive dose needed for clinical therapy, which increases lethal risk for intracranial hemorrhage. Here, a near-infrared-triggered, controlledrelease system, using gold@mesoporous silica core-shell nanospheres (Au@MSNs) with phase-changed material 1-tetradecanol, is formulated to release urokinase plasminogen activators (uPA) on demand. The prepared system presents a sensitive system for releasing uPA, owing to an elevated temperature created by Au@MSNs-induced photothermal effect. For in vitro study, a 3D printed vein vasculature is designed and fabricated to simulate the thrombolysis of system in blood vessel. Murine tail thrombus model is also built to evaluate thrombolysis in vivo. Consequently, localized hyperthermia is validated to possess an effective enhancement for thrombolysis. Therefore, according to the results, the fabricated system demonstrates two aspects of potential superiority: controlled uPA release for reducing risk of side effects, and hyperthermia-enhanced thrombolysis locally for decreasing drug dosage. Assisted with thermal thrombolysis, the present formulated system shows a high efficiency, on-demand drug release, and thus a safer protocol for thrombolytic therapy, which fits the developing trends of precision medicine.

Inhibition of Inflammation‐Associated Thrombosis with ROS‐Responsive Heparin‐DOCA/PVAX Nanoparticles

“…The anti‐inflammatory and anti‐thrombotic capability of nanoparticles is evaluated in a murine tail thrombus model induced with carrageenan . Female Kunming (KM) mice are divided into six groups and treated with PBS, heparin sodium, Hep‐DOCA, tirofiban, HDP‐2, HDP‐4, respectively.…”

“…Carrageenan injection also causes high coagulation state in the blood and venous thrombosis in the tail . Black tails on PBS‐pretreated mice are observed after 24 h carrageenan injection at dose of 15 mg kg −1 .…”

“…All animal procedures were performed according to the protocol approved by the Institutional Animal Care and Use Committee of China. A murine tail thrombus model was built according to previous work with slight modification . A total of 30 female Kunming (KM) mice (20–30 g) with tails longer than 10 cm were divided randomly into five groups and treated with PBS, heparin sodium, Hep‐DOCA, Hep‐DOCA/PVAX, and tirofiban via intravenous injection.…”

“…Thromboembolism, a familiar complication with an acute risk for postoperative patients, is a main source of mortalities and morbidities worldwide. The thromboembolism has mainly given rise to the rupture of an unstable atherosclerotic plaque leading to myocardial infarction or stroke . The thromboembolism is typically associated with inflammation.…”

Shear-, Sound-, and Light-Sensitive Nanoparticles for Thrombolytic Drug Delivery

“…37 Recently, for realizing on-demand thrombolytic agent release, our research group presented a near-infrared-triggered and noninvasive drug delivery system based on gold@mesoporous silica core-shell nanospheres with phase-changed materials 1-tetradecanol for releasing urokinase. 38 Hyperthermia induced by the photothermal effect of gold nanoparticles via near infrared laser (808 nm) not only triggered the release of urokinase but also enhanced a localized thrombolysis. 38 Overall, there are few reported studies on light-sensitive drug delivery system for thrombolysis, but it is hoped that this will become a safe and noninvasive thrombolytic approach in the future after resolving the residual problems.…”