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RGD修饰的吲哚菁绿胶束对胃癌的靶向荧光成像

Targeting Fluorescence Imaging of RGD-Modified Indocyanine Green Micelles on Gastric Cancer.

作者信息

Shao Jun, Zheng Xiaoming, Feng Longbao, Lan Tianyun, Ding Dongbing, Cai Zikai, Zhu Xudong, Liang Rongpu, Wei Bo

机构信息

Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Department of Biomedical Engineering, Ji'nan University, Guangzhou, China.

出版信息

Front Bioeng Biotechnol. 2020 Sep 25;8:575365. doi: 10.3389/fbioe.2020.575365. eCollection 2020.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e217/7546337/e4c22b808196/fbioe-08-575365-g008.jpg

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