Aasen Synnøve Nymark, Pospisilova Aneta, Eichler Tilo Wolf, Panek Jiri, Hruby Martin, Stepanek Petr, Spriet Endy, Jirak Daniel, Skaftnesmo Kai Ove, Thorsen Frits
NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.
Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 162 06 Prague, Czech Republic.
Int J Mol Sci. 2015 Sep 8;16(9):21658-80. doi: 10.3390/ijms160921658.
To facilitate efficient drug delivery to tumor tissue, several nanomaterials have been designed, with combined diagnostic and therapeutic properties. In this work, we carried out fundamental in vitro and in vivo experiments to assess the labeling efficacy of our novel theranostic nanoprobe, consisting of glycogen conjugated with a red fluorescent probe and gadolinium. Microscopy and resazurin viability assays were used to study cell labeling and cell viability in human metastatic melanoma cell lines. Fluorescence lifetime correlation spectroscopy (FLCS) was done to investigate nanoprobe stability. Magnetic resonance imaging (MRI) was performed to study T₁ relaxivity in vitro, and contrast enhancement in a subcutaneous in vivo tumor model. Efficient cell labeling was demonstrated, while cell viability, cell migration, and cell growth was not affected. FLCS showed that the nanoprobe did not degrade in blood plasma. MRI demonstrated that down to 750 cells/μL of labeled cells in agar phantoms could be detected. In vivo MRI showed that contrast enhancement in tumors was comparable between Omniscan contrast agent and the nanoprobe. In conclusion, we demonstrate for the first time that a non-toxic glycogen-based nanoprobe may effectively visualize tumor cells and tissue, and, in future experiments, we will investigate its therapeutic potential by conjugating therapeutic compounds to the nanoprobe.
为促进药物有效递送至肿瘤组织,人们设计了多种具有诊断和治疗双重特性的纳米材料。在本研究中,我们开展了基础的体外和体内实验,以评估我们新型的诊疗纳米探针的标记效果,该探针由与红色荧光探针及钆结合的糖原组成。利用显微镜检查和刃天青活力测定法研究人转移性黑色素瘤细胞系中的细胞标记和细胞活力。采用荧光寿命相关光谱法(FLCS)研究纳米探针的稳定性。进行磁共振成像(MRI)以研究体外T₁弛豫率以及皮下体内肿瘤模型中的对比增强情况。结果表明纳米探针能有效标记细胞,同时不影响细胞活力、细胞迁移和细胞生长。FLCS显示纳米探针在血浆中不会降解。MRI表明在琼脂模型中可检测到低至750个细胞/μL的标记细胞。体内MRI显示,肿瘤中的对比增强在欧乃影造影剂和纳米探针之间具有可比性。总之,我们首次证明一种无毒的基于糖原的纳米探针可有效使肿瘤细胞和组织可视化,并且在未来实验中,我们将通过将治疗性化合物与纳米探针偶联来研究其治疗潜力。