Near-Infrared Light Activated Thermosensitive Ion Channel to Remotely Control Transgene System for Thrombolysis Therapy
Near-Infrared Light Activated Thermosensitive Ion Channel to Remotely Control Transgene System for Thrombolysis Therapy
复制标题
近红外光激活热敏离子通道远程控制溶栓治疗转基因系统
DOI：
10.1002/smll.201901176
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发表时间：
2019
期刊：
影响因子：
13.3
通讯作者：
Yang Huanghao
中科院分区：
文献类型：
--
作者：
Zhang Da;Zhang Cuilin;Lan Shanyou;Huang Yanbing;Liu Jingfeng;Li Juan;Liu Xiaolong;Yang Huanghao
目前的抗血栓治疗策略通常会出现严重的血栓后综合征（PTS），长期每日皮下注射不方便，循环时间短，伴有颅内出血的剂量依赖性风险。针对非侵入性、按需和持续的抗血栓治疗，已经开发了一种基于转基因系统的新的溶栓方法，以通过生物工程细胞远程和精确地控制尿激酶纤溶酶原激活剂（uPA）的表达，用于体外和体内的抗血栓治疗。在这种设计中，近红外（NIR）光可以激活热敏TRPV1通道的表达，以响应光热响应纳米转换器，从而触发合成信号通路来分泌uPA。通过将生物工程细胞包封在可注射水凝胶中以确保长期存活和注射方便，工程细胞可以通过NIR激光无创和精确地原位控制uPA蛋白的产生，从而通过时空控制局部温度来显著增强溶栓治疗效果，无论是在微流体血液循环模拟物还是鼠尾血栓模型中。这种新的溶栓方法可以克服与传统抗血栓治疗相关的一些关键限制，从而为通过人工设计的信号传导开发远程和精确可控的连续溶栓开辟了新的方向。
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.