Department of Radiology and Nuclear Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Immunogenetic Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Eur J Pharm Sci. 2020 May 30;148:105312. doi: 10.1016/j.ejps.2020.105312. Epub 2020 Mar 17.
Exosomes represent unique features including nontoxicity, non-immunogenicity, biodegradability, and targeting ability that make them suitable candidates for clinical applications. Therefore, in this study, Tc-radiolabel HER2 targeted exosomes (Tc-exosomes) were provided for tumor imaging. These exomes are obtained from genetically engineered cells and possessed DARPin G3 as a ligand for HER2 receptors. These exosomes were radiolabeled using fac-[Tc(CO)(HO)] synthon. The quality control showed high radiochemical purity (RCP) for Tc-exosomes (>96%). Tc-exosomes displayed a higher affinity toward SKOV-3 cells (higher HER2 expression) in comparison with MCF-7, HT29, U87-MG, A549 cell lines at different levels of HER2 expression. Trastuzumab (an antibody with a high affinity toward HER2) inhibited the binding of Tc-exosomes to SKOV-3 cells up to 40%. Biodistribution study in SKOV-3 tumor bearing nude mice confirmed the ability of Tc-exosomes for accumulation in the tumor. Tc-exosomes can visualize tumor in SKOV-3 tumor-bearing nude mouse. The blockage of HER2 receptors using trastuzumab (excessive amount) suggests the Tc-exosomes binding to the receptors and reduced the accumulation of Tc-exosomes in the tumor site. This suggest that Tc-exosomes interact with HER2 receptors and act through specific targeting.
外泌体具有独特的特性，包括低毒性、非免疫原性、可生物降解性和靶向能力，使其成为临床应用的理想候选者。因此，在本研究中，我们提供了 Tc 放射性标记 HER2 靶向外泌体（Tc-exosomes）用于肿瘤成像。这些外泌体是从基因工程细胞中获得的，具有 DARPin G3 作为 HER2 受体的配体。这些外泌体使用 fac-[Tc(CO)(HO)] 合成物进行放射性标记。质量控制表明，Tc-exosomes 的放射化学纯度（RCP）非常高（>96%）。与 MCF-7、HT29、U87-MG、A549 细胞系相比，Tc-exosomes 对 SKOV-3 细胞（HER2 表达较高）具有更高的亲和力，而不同 HER2 表达水平的细胞系对 Tc-exosomes 的亲和力则较低。曲妥珠单抗（一种对 HER2 具有高亲和力的抗体）可抑制 Tc-exosomes 与 SKOV-3 细胞的结合，抑制率高达 40%。在 SKOV-3 荷瘤裸鼠的体内分布研究中，证实了 Tc-exosomes 在肿瘤中的积累能力。Tc-exosomes 可以在 SKOV-3 荷瘤裸鼠中可视化肿瘤。使用曲妥珠单抗（过量）阻断 HER2 受体表明 Tc-exosomes 与受体结合，并减少 Tc-exosomes 在肿瘤部位的积累。这表明 Tc-exosomes 与 HER2 受体相互作用，并通过特异性靶向发挥作用。
