5 years ago

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

Near-Infrared Triggered Release of uPA from Nanospheres for Localized Hyperthermia-Enhanced Thrombolysis
Shuhua Wang, Mengke Liu, Kui Hong, Xiaolei Wang, Xingwei Ding, Ying Liu, Hongbo Xin, Chaochao Wei, Weimin Zhou, Ting Yang
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, controlled-release 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. A near-infrared (NIR)-laser-triggered release urokinase plasminogen activators (uPA) delivery system based on gold@mesoporous silica core–shell nanospheres is fabricated for thrombolytic therapy. The loaded uPA can be triggered to release from the system on demand via NIR laser irradiation owing to the phase change of 1-tetradecanol. More importantly, localized hyperthermia, induced by photothermal transformation of gold nanoparticles, can enhance the lysis of clots.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201701824

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