| 摘要: |
| 目的 探讨相变型（PT）纳米粒（NPs）靶向动脉血栓深度及其与体外溶栓效果的相关性。方法 通过双乳化法制备一种靶向纤维蛋白的PLGA-PFH-CREKA NPs，验证其理化特性。采集新西兰大白兔的动脉血制作动脉血栓，分别置于荧光标记的靶向PT、非靶向PT、靶向载双蒸水（NPT）的NPs中，并用1 W/cm2声功率密度的低强度聚焦超声（LIFU）辐照，记录前后的质量，计算溶栓率，同时将处理后的血凝块制成切片，通过共聚焦显微镜观察、测量穿透深度，线性回归分析穿透深度与溶栓率的相关性。建立SD大鼠腹主动脉血栓模型，采用靶向PT、非靶向PT NPs评价体内靶向能力。结果 制备的靶向纤维蛋白的PT NPs平均粒径（297.8±11.82）nm，表面电位（1.44±0.22）mV，结构呈均匀球形，分散性好；体外溶栓实验发现靶向PT组与非靶向PT组、NPT组的溶栓率差异有统计学意义（F=108.508，P<0.001）；靶向PT组对血栓的穿透性相较于非靶向PT组、NPT组差异有统计学意义（F=96.187，P<0.001），线性回归发现靶向PT组对血栓穿透深度与溶栓率呈正相关（R2=0.818，P<0.05）。在SD大鼠腹主动脉血栓模型观察到靶向相变组较非靶向相变组对血栓的靶向性更好。 结论 靶向纤维蛋白的相变型NPs，对血栓纤维蛋白有良好的靶向性，有较好的溶栓效果，对血栓有很好的穿透性，并且相变所致溶栓率与血栓穿透深度呈正相关。 |
| 关键词: 相变纳米粒 分子影像 动脉血栓 穿透性 |
| DOI： |
| 投稿时间：2021-01-24修订日期：2021-02-15 |
| 基金项目:中国博士后科学基金 |
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| Experimental study on the correlation between the targeting depth and the thrombolytic efficacy of phase-transitional nanoparticles in arterial thrombosis |
| Zhong Yixin,Ye Man,Xu Jie,Zhang Wenli,Hu Liu,Fang Ni,Guo Dajing |
| (The second affiliated hospital of Chongqing medical university;Second Affiliated Hospital of Chongqing Medical University) |
| Abstract: |
| Object To investigate the correlation between the targeted depth and thrombolytic effect of fibrin-targeted liquid-gas phase-transitional (PT) nanoparticles (NPs) in arterial thrombosis. Methods Fibrin targeted PLGA-PFH-CREKA NPs was developed by double emulsification method, and its physical and chemical properties were verified. The preparation of arterial thrombosis were acquired through the New Zealand white rabbit, then the thrombi were collected in the non-phase-transitional (NPT) NPs, PT and non-targeted PT NPs respectively, LIFU with sound power density of 1 W/cm2 was used to irradiate outside. The quality of thrombi were recorded before and after the experiment, and frozen sections of blood clot were used to measure penetration depth by confocal microscope, the correlation between thrombolytic rate and the penetration depth of NPs was analyzed by linear regression analysis. Then the abdominal aortic thrombosis model was established in SD rats, fibrin targeted PT, non-targeted PT NPs were used to injected through rat tail vein respectively to evaluate the targeting ability in vivo. Result The PT fibrin targeted NPs were successfully prepared with a particle of 297.8±11.82 nm and a surface Zeta potential of 1.44±0.22 mV. This NPs also have a uniform spherical structure with good dispersibility. The thrombolysis rate (F=108.508，P<0.001) and penetration (F=96.187, P<0.001) of thrombus in the targeted PT group was significantly different from that in the non-targeted PT and NPT group. Moreover, linear regression showed a positive correlation between thrombus penetration depth and thrombolytic rate in the targeted PT group (R2=0.818, P<0.05). In the SD rat model of abdominal aortic thrombosis, the targeted PT group showed better fibrin targeting than the non-targeted PT group. Conclusion In this study, the targeting fibrin PT NPs were successfully prepared, which have a good targeting effect to thrombus fibrin, good thrombolytic effect, and good penetration to thrombus. Meanwhile, the thrombolytic rate is positively correlated with the penetration depth of thrombus in PT group. |
| Key words: Phase-Transitional Nanoparticle Molecular Imaging Arterial Thrombus Penetrability |
