金纳米棒@全氟化碳微泡用于肺癌的超灵敏129Xe/19F双核 MRI 及光声成像研究

As a malignant tumor with the highest morbidity and mortality in China, lung cancer has been given rising attentions along with environmental deterioration. Development of comprehensive and reliable technique for early diagnosis and therapy are the key to cure lung cancer. We evaluated a light-responsive biodegradable nanocomposite AuNRs@MSN-129Xe/PFP as candidate nanoplatforms for multifunctional loading. It is strategically designed and prepared for ultrasensitive 129Xe/19F NMR/MRI/photoacoustic (PAI) dual-modality imaging guided photothermal therapy of lung cancer. Upon 808 nm laser irradiation, the loaded PFP will undergo a liquid–gas phase transition due to the heat generation from AuNRs, thus generating nanobubbles followed by the coalescence into microbubbles. The conversion of nanobubbles to microbubbles can enhance the tumor targeted 129Xe T1 weighted and 19F T2 weighted MR signals. This nanotheranostic platform exhibits excellent biocompatibility and biodegradability, distinct gas bubbling phenomenon, good MR/PA imaging contrast, and remarkable photothermal efficiency.

肺癌是我国发病率和死亡率第一的恶性肿瘤，发展精准诊疗技术是提高存活率的关键手段。MRI是癌症检测和治疗评估的重要影像学技术，但传统1H MRI灵敏度较低，且单一核素很难全面、多视角的获得疾病信息。本课题组在国内首次实现了磁共振信号增强倍数大于50000倍的人体肺部超灵敏磁共振成像（129Xe MRI），也进行了一系列19F MRI的活体研究。本项目拟对非小细胞肺癌进行超灵敏129Xe/19F活体双核素MRI研究；利用AuNRs@MSN包裹的129Xe/PFP为载体，在近红外波长的小功率激光照射下，AuNRs产生光热效应，对肺癌细胞和实体肿瘤进行光热治疗的同时，也触发了129Xe/PFP的相变并产生纳米微泡。微泡中的129Xe/19F可同时增强超灵敏129Xe的T1和19F的T2加权信号，从而获得肿瘤组织多核MRI的全视角成像信息，实现T1/T2加权对比度协同增强的双核MRI诊疗一体化技术。

本项目构建了一种合成简单的多通道超灵敏核磁共振分子探针；同时对肺癌细胞及活体组织进行129Xe NMR/MRI及19F NMR/MRI的谱学及成像分析，为超灵敏磁共振分子影像提供一种新工具；将其扩展至其他成像模式（如光声成像等），探索其在多模态成像中的应用潜力，并利用光热治疗（PTT）实现对肺癌的高效、靶向联合治疗。该方法对非小细胞肺癌进行了超灵敏129Xe/19F活体双核素MRI研究，获得肿瘤组织多核MRI的全视角成像信息，实现了一种对比度协同增强的双核MRI诊疗一体化技术。