Luciano Michael, Erfanzadeh Mohsen, Zhou Feifei, Zhu Hua, Bornhütter Tobias, Röder Beate, Zhu Quing, Brückner Christian
Department of Chemistry, University of Connecticut, Storrs, CT 06269-3060, USA.
Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269-4157, USA.
Org Biomol Chem. 2017 Jan 25;15(4):972-983. doi: 10.1039/c6ob02640k.
The synthesis and photophysical properties of a tetra-PEG-modified and freely water-soluble quinoline-annulated porphyrin are described. We previously demonstrated the ability of quinoline-annulated porphyrins to act as an in vitro NIR photoacoustic imaging (PAI) contrast agent. The solubility of the quinoline-annulated porphyrin derivative in serum now allowed the assessment of the efficacy of the PEGylated derivative as an in vivo NIR contrast agent for the PAI of an implanted tumor in a mouse model. A multi-fold contrast enhancement when compared to the benchmark dye ICG could be shown, a finding that could be traced to its photophysical properties (short triplet lifetimes, low fluorescence and singlet oxygen sensitization quantum yields). A NIR excitation wavelength of 790 nm could be used, fully taking advantage of the optical window of tissue. Rapid renal clearance of the dye was observed. Its straight-forward synthesis, optical properties with the possibility for further optical fine-tuning, nontoxicity, favorable elimination rates, and contrast enhancement make this a promising PAI contrast agent. The ability to conjugate the PAI chromophore with a fluorescent tag using a facile and general conjugation strategy was also demonstrated.
描述了一种四聚乙二醇修饰且可自由溶于水的喹啉稠合卟啉的合成及其光物理性质。我们之前已证明喹啉稠合卟啉能够作为体外近红外光声成像（PAI）造影剂。喹啉稠合卟啉衍生物在血清中的溶解度使得能够评估聚乙二醇化衍生物作为体内近红外造影剂用于小鼠模型中植入肿瘤的PAI的功效。与基准染料吲哚菁绿（ICG）相比，可显示出多重对比度增强，这一发现可追溯至其光物理性质（短三重态寿命、低荧光和单线态氧敏化量子产率）。可使用790 nm的近红外激发波长，充分利用组织的光学窗口。观察到该染料通过肾脏快速清除。其简单的合成方法、具有进一步光学微调可能性的光学性质、无毒性、良好的清除率以及对比度增强使其成为一种有前景的PAI造影剂。还展示了使用简便通用的共轭策略将PAI发色团与荧光标签共轭的能力。
