Shao Jun, Zheng Xiaoming, Feng Longbao, Lan Tianyun, Ding Dongbing, Cai Zikai, Zhu Xudong, Liang Rongpu, Wei Bo
Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Biomedical Engineering, Ji'nan University, Guangzhou, China.
Front Bioeng Biotechnol. 2020 Sep 25;8:575365. doi: 10.3389/fbioe.2020.575365. eCollection 2020.
Early diagnosis and complete resection of the tumor is an important way to improve the quality of life of patients with gastric cancer. In recent years, near-infrared (NIR) materials show great potential in fluorescence-based imaging of the tumors. To realize a satisfying intraoperative fluorescence tumor imaging, there are two pre-requirements. One is to obtain a stable agent with a relatively longer circulation time. The second is to make it good biocompatible and specific targeting to the tumor. Here, we developed an RGD-modified Distearyl acylphosphatidyl ethanolamine-polyethylene glycol micelle (DSPE-PEG-RGD) to encapsulate indocyanine green (ICG) for targeting fluorescence imaging of gastric cancer, aimed at realizing tumor-targeted accumulation and NIR imaging. H NMR spectroscopy confirmed its molecular structure. The characteristics and stability results indicated that the DSPE-PEG-RGD@ICG had a relatively uniform size of <200 nm and longer-term fluorescence stability. RGD peptides had a high affinity to integrin αβ and the specific targeting effect on SGC7901 was assessed by confocal microscopy . Additionally, the results of cytotoxicity and blood compatibility were consistent with the acute toxicity test , which revealed good biocompatibility. The biodistribution and tumor targeting image of DSPE-PEG-RGD@ICG were observed by an imaging system in tumor-bearing mice. DSPE-PEG-RGD@ICG demonstrated an improved accumulation in tumors and longer circulation time when compared with free ICG or DSPE-PEG@ICG. In all, DSPE-PEG-RGD@ICG demonstrated ideal properties for tumor target imaging, thus, providing a promising way for the detection and accurate resection of gastric cancer.
早期诊断并完整切除肿瘤是提高胃癌患者生活质量的重要途径。近年来,近红外(NIR)材料在肿瘤的荧光成像中显示出巨大潜力。为实现令人满意的术中荧光肿瘤成像,有两个前提条件。一是获得具有相对较长循环时间的稳定试剂。二是使其具有良好的生物相容性并对肿瘤具有特异性靶向性。在此,我们开发了一种RGD修饰的二硬脂酰基磷脂酰乙醇胺-聚乙二醇胶束(DSPE-PEG-RGD)来包裹吲哚菁绿(ICG)用于胃癌的靶向荧光成像,旨在实现肿瘤靶向聚集和近红外成像。核磁共振氢谱证实了其分子结构。特性和稳定性结果表明,DSPE-PEG-RGD@ICG具有相对均匀的尺寸<200 nm且具有长期荧光稳定性。RGD肽对整合素αβ具有高亲和力,通过共聚焦显微镜评估其对SGC7901的特异性靶向作用。此外,细胞毒性和血液相容性结果与急性毒性试验一致,显示出良好的生物相容性。通过成像系统在荷瘤小鼠中观察DSPE-PEG-RGD@ICG的生物分布和肿瘤靶向成像。与游离ICG或DSPE-PEG@ICG相比,DSPE-PEG-RGD@ICG在肿瘤中的蓄积有所改善且循环时间更长。总之,DSPE-PEG-RGD@ICG表现出理想的肿瘤靶向成像特性,从而为胃癌的检测和精确切除提供了一种有前景的方法。