Thrombus-targeted nano-agents for NIR-II diagnostic fluorescence imaging-guided flap thromboembolism multi-model therapy.
Thrombus-targeted nano-agents for NIR-II diagnostic fluorescence imaging-guided flap thromboembolism multi-model therapy.
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DOI：
10.1186/s12951-022-01649-6
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发表时间：
2022-10-14
影响因子：
10.2
通讯作者：
Han, Wei
中科院分区：
文献类型：
--
作者：
Cao, Zichen;Zhang, Xinyu;Wei, Zheng;Song, Chuanhui;Zou, Huihui;Ran, Jianchuan;Zhang, Hongbo;Xie, Diya;Han, Shengwei;Wang, Yufeng;Cai, Yu;Han, Wei
在口腔颌面外科手术中，皮瓣修复对于术后生活质量至关重要。尽管如此，血栓形成对于皮瓣的存活来说是致命的。此外，一些术后血栓性疾病，如肺栓塞，也威胁着患者的生命。传统的诊断方法仍然受到大量硬件的限制，存在不便、延迟和主观性等问题。此外，治疗主要依靠溶栓药物，如尿激酶（UK）纤溶酶原激活剂，可能会导致出血风险，尤其是脑出血。在此，我们开发了一种以第一近红外窗口（NIR-I）光治疗剂Y8和尿激酶纤溶酶原激活剂（UK）为核心，并用纤维蛋白靶向肽Gly–Pro–Arg–Pro–Pro（GPRPP）修饰的聚乳酸-乙醇酸（PLGA）纳米颗粒（NPs），用于皮瓣和术后血栓栓塞治疗（命名为GPRPP-Y8U@P）。共轭分子Y8赋予GPRPP-Y8U@P近红外-II成像能力和优异的光热/光动力治疗效果。体内实验证明GPRPP-Y8U@P可以通过NIR-II荧光成像快速定位血栓，并对栓塞血管石蜡切片的半定量分析验证了其溶栓效率。此外，捕获在纳米粒子中的尿激酶不会导致非特异性出血，极大地提高了身体安全性和疗效，同时最大限度地减少了副作用。总体而言，GPRPP-Y8U@P的优势，例如血栓精确定位、血栓在位消融以及轻微副作用，证明了该方法对于血栓治疗的有效临床监测的吸引力。在线版本包含可在 10.1186/s12951-022-01649-6 获取的补充材料。
In oral and maxillofacial surgery, flap repair is essential to the quality of postoperative life. Still, thrombosis is fatal for the survival of the flaps. Besides, some postoperative thrombotic diseases, such as pulmonary embolism, also intimidate patients’ life. The traditional diagnostic methods are still limited by a large amount of hardware and suffer from inconvenience, delay, and subjectivity. Moreover, the treatments mainly rely upon thrombolytics, such as urokinase (UK) plasminogen activator, which may cause bleeding risk, especially intracerebral hemorrhage. Herein, a kind of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing a first near-infrared window (NIR-I) phototheranostic agent Y8 and urokinase plasminogen activator (UK) as the core, and modified with the fibrin-targeting peptide Gly–Pro–Arg–Pro–Pro (GPRPP) were developed for the flap and postoperative thromboembolism treatment (named GPRPP-Y8U@P). The conjugated molecule Y8 endows GPRPP-Y8U@P with the capacity of NIR-II imaging and excellent photothermal/photodynamic therapeutic effects. In vivo experiments demonstrated that GPRPP-Y8U@P could quickly locate thrombus by NIR-II fluorescence imaging, and semi-quantitative analysis of the embolized blood vessels' paraffin section verified its thrombolytic efficiency. Additionally, the urokinase trapped in the NPs would not result in nonspecific bleeding, tremendously improving physical security and curative effects with minimizing side effects. Overall, the advantages of GPRPP-Y8U@P, such as precise localization of the thrombus, thrombus ablation in the site, and mild side effects, demonstrated the attractiveness of this approach for effective clinical monitoring of thrombus therapy. The online version contains supplementary material available at 10.1186/s12951-022-01649-6.
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影响因子：
18.9
作者：
Hou J;Zhou J;Chang M;Bao G;Xu J;Ye M;Zhong Y;Liu S;Wang J;Zhang W;Ran H;Wang Z;Chen Y;Guo D
通讯作者：
Guo D
非规范自噬抑制自身炎症，类似狼疮的对垂死细胞的反应。
影响因子：
64.8
作者：
Martinez J;Cunha LD;Park S;Yang M;Lu Q;Orchard R;Li QZ;Yan M;Janke L;Guy C;Linkermann A;Virgin HW;Green DR
通讯作者：
Green DR
影响因子：
13.6
作者：
Lee HP;Alisafaei F;Adebawale K;Chang J;Shenoy VB;Chaudhuri O
通讯作者：
Chaudhuri O
影响因子：
1.9
作者：
Gerressen, Marcus;Pastaschek, Claudia Inge;Ghassemi, Alireza
通讯作者：
Ghassemi, Alireza
影响因子：
20.3
作者：
Beristain-Covarrubias, Nonantzin;Perez-Toledo, Marisol;Cunningham, Adam F.
通讯作者：
Cunningham, Adam F.