Targeted Bioluminescent Imaging of Pancreatic Ductal Adenocarcinoma Using Nanocarrier-Complexed EGFR-Binding Affibody-Gaussia Luciferase Fusion Protein.
Targeted Bioluminescent Imaging of Pancreatic Ductal Adenocarcinoma Using Nanocarrier-Complexed EGFR-Binding Affibody-Gaussia Luciferase Fusion Protein.
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DOI：
10.3390/pharmaceutics15071976
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发表时间：
2023-07-19
期刊：
影响因子：
5.4
通讯作者：
中科院分区：
文献类型：
--
作者：
体内成像在生物学研究中取得了令人印象深刻的进展，无论是临床前还是临床，研究人员都有一系列可用的成像方法。生物发光成像是体内研究的一种有利方法，它允许简单地获取低背景信号的图像。研究人员一直在寻找改善生物发光成像在体内应用的方法，我们试图通过开发一种能够特异性靶向感兴趣细胞的生物发光探针来实现这一目标。我们选择胰腺导管腺癌（PDAC）作为疾病模型，因为它是最常见的胰腺癌类型，生存率极低。我们以胰腺癌细胞中经常过度表达的表皮生长因子受体（EGFR）为目标，使用EGFR特异性的附着体选择性地鉴定PDAC细胞，并通过工程设计一种与附着体和生物发光蛋白融合的蛋白，传递一种高斯荧光素酶（GLuc）生物发光蛋白用于成像。然后将该融合蛋白与G5-PAMAM树状大分子纳米载体络合。树状大分子用于提高蛋白质在体内的稳定性和增加信号强度。我们的靶向生物发光复合物在体外增强了对PDAC细胞的摄取，并在体内定位于胰腺癌异种移植小鼠的PDAC肿瘤。生物发光复合物可以描绘肿瘤形状，识别多个肿块，定位转移灶。通过这项工作，一种靶向egfr的生物发光树突状复合物能够在临床前模型中直接识别和成像胰腺癌细胞。这证明了靶向纳米载体介导的生物发光蛋白递送是一种改善体内生物发光成像的方法。
In vivo imaging has enabled impressive advances in biological research, both preclinical and clinical, and researchers have an arsenal of imaging methods available. Bioluminescence imaging is an advantageous method for in vivo studies that allows for the simple acquisition of images with low background signals. Researchers have increasingly been looking for ways to improve bioluminescent imaging for in vivo applications, which we sought to achieve by developing a bioluminescent probe that could specifically target cells of interest. We chose pancreatic ductal adenocarcinoma (PDAC) as the disease model because it is the most common type of pancreatic cancer and has an extremely low survival rate. We targeted the epidermal growth factor receptor (EGFR), which is frequently overexpressed in pancreatic cancer cells, using an EGFR-specific affibody to selectively identify PDAC cells and delivered a Gaussia luciferase (GLuc) bioluminescent protein for imaging by engineering a fusion protein with both the affibody and the bioluminescent protein. This fusion protein was then complexed with a G5-PAMAM dendrimer nanocarrier. The dendrimer was used to improve the protein stability in vivo and increase signal strength. Our targeted bioluminescent complex had an enhanced uptake into PDAC cells in vitro and localized to PDAC tumors in vivo in pancreatic cancer xenograft mice. The bioluminescent complexes could delineate the tumor shape, identify multiple masses, and locate metastases. Through this work, an EGFR-targeted bioluminescent–dendrimer complex enabled the straightforward identification and imaging of pancreatic cancer cells in vivo in preclinical models. This argues for the targeted nanocarrier-mediated delivery of bioluminescent proteins as a way to improve in vivo bioluminescent imaging.
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影响因子：
5.2
作者：
Leroux C;Konstantinidou G
通讯作者：
Konstantinidou G
影响因子：
5.2
作者：
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通讯作者：
Sanglard D
影响因子：
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通讯作者：
Deo SK
影响因子：
4.6
作者：
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通讯作者：
Deo, Sapna K.
影响因子：
7.4
作者：
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Tao, Hiroaki