Erythrocyte-membrane-camouflaged magnetic nanocapsules with photothermal/magnetothermal effects for thrombolysis.

Venous/arterial thrombosis poses significant threats to human health. However, drug-enabled thrombolysis treatment often encounters challenges such as a short half-life and low bioavailability. To address these issues, we report the design of erythrocyte-membrane (EM) camouflaged nanocapsules (USIO/UK@EM) incorporating ultra-small iron oxide (USIO) and urokinase (UK) drug, which exhibit remarkable photothermal/magnetothermal effects and drug delivery ability for venous and arterial thrombolysis. USIO, UK, and EM were coextruded to fabricate USIO/UK@EM with average sizes of 103.7 nm. Since USIO/UK@EM possesses wide photoabsorption characteristics and good magnetic properties, its solution demonstrates a remarkable temperature increase to 41.8-42.9 °C within 5 min when exposed to an 808 nm laser (0.33 mW cm-2 ) or an alternating magnetic field (AMF). Such photothermal/magnetothermal effect along with UK confers impressive thrombolytic rates of 82.4% and 74.2%, higher than that (∼15%) achieved by UK alone. Furthermore, the EM coating extends the circulating half-life (t1/2 = 3.28 h). When USIO/UK@EM are administered to mice and rabbits, tail vein thrombus in mice and femoral artery thrombus in rabbits can be dissolved by the synergetic effect of thermothrombolysis and UK. Therefore, this study not only offers insights into the rational design of multifunctional biomimetic nanocapsules but also showcases a promising thrombolysis strategy utilizing nanomedicine. This article is protected by copyright. All rights reserved.