Near‐Infrared Light Activated Thermosensitive Ion Channel to Remotely Control Transgene System for Thrombolysis Therapy

Abstract

Current antithrombotic therapeutic strategies often suffer from severe post‐thrombotic syndromes (PTS), inconvenient daily subcutaneous injections for a long time and short circulation times accompanied by a dose‐dependent risk of intracranial hemorrhage. Aiming at noninvasive, on‐demand, and sustained antithrombotic therapy, a new thrombolysis approach based on the transgene system has been developed to remotely and precisely control the expression of urokinase plasminogen activator (uPA) by bioengineered cells for antithrombotic therapy both in vitro and in vivo. In this design, the near‐infrared (NIR) light could activate the expression of the thermosensitive TRPV1 channel in response to photothermal responsive nanotransducers to trigger the synthetic signaling pathway to secret uPA. By encapsulating bioengineered cells in injectable hydrogel to ensure long‐term survival and convenience for injection, the engineered cells could noninvasively and precisely control the production of uPA protein in situ via an NIR laser to significantly enhance the thrombolysis therapeutic effects by spatiotemporally controlling the local temperature, in both the microfluidic blood circulation mimic and the murine tail thrombus model. This novel thrombolysis approach could overcome some key limitations that are associated with conventional antithrombotic therapy, thus opening a new direction for developing remotely and precisely controllable continuous thrombolysis through artificially designed signaling.

Guiding Drug Through Interrupted Bloodstream for Potentiated Thrombolysis by C‐Shaped Magnetic Actuation System In Vivo

“…[9][10][11] Additionally, light-mediated nanoplatforms were deployed for photothermal and photodynamic thrombus therapy through the generation of hyperthermia and reactive oxygen species; this resulted in accelerated drug release and improved thrombolytic efficacy. [12][13][14] Despite promising results, these strategies are limited by tissue damage caused by physical effects, and they have not been implemented in clinical practice. [15] Therefore, it is worth engineering a distinct design strategy with simplified structures but an efficient delivery of the tPA through an Fast and effective thrombolysis using tissue plasminogen activator (tPA) is limited by the poor delivery efficiency of thrombolytic drugs, which is induced by an interrupted bloodstream and delayed recanalization.…”

Sequential Release Platform of Heparin and Urokinase with Dual Physical (NIR-II and Bubbles) Assistance for Deep Venous Thrombosis

“…Deep vein thrombosis (DVT) seriously endangers human health, and its morbidity, mortality, and disability rates are still high. − At present, thrombolytic therapy is one of the effective methods for the treatment of DVT, and systemic thrombolysis is mainly performed through peripheral veins in the clinic. − However, the main drawback of urokinase (UK) is its short cycling half-life (9–12 min), resulting in a relatively weak thrombolytic effect when administered at low doses, while a high dose or overdose will increase the potential risk of death from intracranial hemorrhage . Reasonably, to overcome the above limitations, an appropriate thrombolysis drug carrier is needed to improve the efficiency from both drug combination and physical assistance, so as to achieve the purpose of effective thrombolysis under a limited dose (risk) of the UK.…”

“…4−6 However, the main drawback of urokinase (UK) is its short cycling half-life (9−12 min), resulting in a relatively weak thrombolytic effect when administered at low doses, while a high dose or overdose will increase the potential risk of death from intracranial hemorrhage. 7 Reasonably, to overcome the above limitations, an appropriate thrombolysis drug carrier is needed to improve the efficiency from both drug combination and physical assistance, so as to achieve the purpose of effective thrombolysis under a limited dose (risk) of the UK.…”

Engineering Gadolinium‐Integrated Tellurium Nanorods for Theory‐Oriented Photonic Hyperthermia in the NIR‐II Biowindow

“…Furthermore, it has been found that the early stages of cancer could be diagnosed by analyzing different imaging (such as computed tomography (CT) and magnetic resonance (MR) imaging) and pathology results. [ 22–26 ] Therefore, the construction of multifunctional nanomaterials could improve the diagnostic rate and therapeutic effect against cancer. [ 27–29 ]…”

“…Furthermore, it has been found that the early stages of cancer could be diagnosed by analyzing different imaging (such as computed tomography (CT) and magnetic resonance (MR) imaging) and pathology results. [22][23][24][25][26] Therefore, the construction of multifunctional nanomaterials could improve the diagnostic rate and therapeutic effect against cancer. [27][28][29] Te nanomaterials have shown promising potentials in photonic hyperthermia of cancer due to the low long-term toxicity, high biocompatibility, and satisfactory therapeutic outcomes.…”