Polydopamine-modified dual-ligand nanoparticles as highly effective and targeted magnetic resonance/photoacoustic dual-modality thrombus imaging agents
Polydopamine-modified dual-ligand nanoparticles as highly effective and targeted magnetic resonance/photoacoustic dual-modality thrombus imaging agents
复制标题
聚多巴胺修饰的双配体纳米颗粒作为高效靶向磁共振/光声双模态血栓显像剂
DOI：
10.2147/ijn.s216603
复制
发表时间：
2019-01-01
影响因子：
8
通讯作者：
Ran, Haitao
中科院分区：
文献类型：
--
作者：
Zhang, Yu;Zhong, Yixin;Ran, Haitao
背景：血小板活化和随后的聚集是血栓形成的初始阶段。一种特异性靶向活化血小板并在体内高剪切应力下保留的分子探针，可以增强成像效果，实现早期、准确的诊断。 方法和材料：在本研究中，我们利用聚多巴胺构建了纳米粒子（NPs），其携带两种肽，同时结合活化血小板上的整合素αIIbβ3和P-选择素，以增强NPs的靶向性。 结果：利用模拟循环装置在体外证明了纳米粒子对红色和白色血栓的靶向特异性和结合稳定性，并通过体内磁共振（MR）/光声（PA）双模态成像研究了纳米粒子对混合血栓的靶向作用。两种肽表面修饰的纳米粒子在体外比单一肽或无肽的纳米粒子对红、白色血栓具有更高的选择性和保留作用，且靶向效果与活化血小板的数量和分布以及血栓的结构和类型密切相关。该纳米颗粒还具有MR/PA双模态成像功能，显着增强了体内混合血栓的成像。结论：这些双靶向纳米颗粒提高了高剪切应力下对不同血栓的靶向特异性和结合稳定性，有利于血栓的早期诊断。
Background: Platelet activation and subsequent aggregation are the initial stages of thrombosis. A molecular probe that specifically targets activated platelets and remains retained under high shear stress in vivo can enhance the imaging effect to achieve early and accurate diagnosis.Methods and materials: In this study, we constructed nanoparticles (NPs) using polydopamine to carry two peptides that simultaneously bind integrin alpha IIb beta 3 and P-selectin on activated platelets to enhance the targeting of NPs to thrombus.Results: The targeting specificity and binding stability of the NPs on red and white thrombi were demonstrated in vitro using a simulated circulatory device and the targeting effect of the NPs on mixed thrombus was studied by magnetic resonance (MR)/photoacoustic (PA) dual-modality imaging in vivo. NPs that were surface modified with both peptides have higher selectivity and retention to red and white thrombi in vitro than NPs with a single or no peptide, and the targeting effect was closely related to the number and distribution of activated platelets as well as the structure and type of thrombus. The NPs also have MR/PA dual-modality imaging functionality, significantly enhancing the imaging of mixed thrombus in vivo.Conclusion: These dual-targeted NPs have improved targeting specificity and binding stability to different thrombi under high shear stress and are beneficial for the early diagnosis of thrombosis.