Xu Sijia, Yang Fei, Zhou Xiao, Zhuang Yaping, Liu Baoxia, Mu Yang, Wang Xing, Shen Hong, Zhi Guang, Wu Decheng
Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, China.
Department of Cardiology, Chinese PLA General Hospital , Beijing 100853, China.
ACS Appl Mater Interfaces. 2015 Sep 16;7(36):20460-8. doi: 10.1021/acsami.5b06594. Epub 2015 Sep 1.
Well-designed agents for enhanced multimodal imaging have attracted great interests in recent years. In this work, we adopted a premix membrane emulsification (PME) method to prepare uniform PEGylated poly(lactic-co-glycolic acid) (PLGA) microcapsules (MCs) with superparamagnetic Fe3O4 nanoparticles (NPs) embedded in the shell (Fe3O4@PEG-PLGA MCs) for ultrasound (US)/magnetic resonance (MR) bimodal imaging. Compared to Fe3O4@PLGA MCs without PEGylation, Fe3O4@PEG-PLGA MCs could more stably and homogeneously disperse in physiological solutions. In vitro and in vivo trials demonstrated that Fe3O4@PEG-PLGA MCs (∼3.7 μm) with very narrow size distribution (PDI=0.03) could function as efficient dual-modality contrast agents to simultaneously enhance US and MR imaging performance greatly. In vitro cell toxicity and careful histological examinations illustrated no appreciable cytotoxicity and embolism of Fe3O4@PEG-PLGA MCs to mice even at high dose. The uniform composite MCs developed here can act as clinical bimodal contrast agents to improve hybrid US/MR imaging contrast, which is promising for accurate diagnosis and real-time monitoring of difficult and complicated diseases.
近年来，设计精良的用于增强多模态成像的试剂引起了极大的关注。在这项工作中，我们采用预混膜乳化（PME）方法制备了均匀的聚乙二醇化聚乳酸-羟基乙酸共聚物（PLGA）微胶囊（MCs），其壳层中嵌入了超顺磁性四氧化三铁纳米颗粒（NPs）（Fe3O4@PEG-PLGA MCs），用于超声（US）/磁共振（MR）双模态成像。与未聚乙二醇化的Fe3O4@PLGA MCs相比，Fe3O4@PEG-PLGA MCs在生理溶液中能更稳定、更均匀地分散。体外和体内试验表明，尺寸分布非常窄（PDI = 0.03）的Fe3O4@PEG-PLGA MCs（约3.7μm）可作为高效的双模态造影剂，同时极大地增强超声和磁共振成像性能。体外细胞毒性和仔细的组织学检查表明，即使在高剂量下，Fe3O4@PEG-PLGA MCs对小鼠也没有明显的细胞毒性和栓塞现象。这里开发的均匀复合微胶囊可作为临床双模态造影剂，以改善超声/磁共振混合成像的对比度，这对于疑难复杂疾病的准确诊断和实时监测具有广阔前景。
