Lanthanide Metallacrowns as Near-Infrared Fluorescent Probes for Optical Imaging

稀土金属冠作为光学成像的近红外荧光探针

• 批准号: 8593456
• 负责人: Evan Ramchandra Trivedi
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-18 至 2015-07-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8593456
• 关键词: Address; Binding; Biocompatible; Biological; Cancer Detection; Cancer Patient; Cell Survival; Cellular biology; Clinic; Complex; Contrast Media; Data; Detection; Development; Diagnosis; Diagnostic; Dyes; Early Diagnosis; Electronics; Encapsulated; Energy Transfer; Exhibits; Fluorescein; Fluorescence; Fluorescent Probes; Future; Hydration status; Hydroxamic Acids; Image; Imaging Techniques; In Vitro; Ions; Lanthanoid Series Elements; Libraries; Ligands; Light; Liquid substance; Magnetic Resonance Imaging; Malignant Neoplasms; Maximum Tolerated Dose; Methods; Modality; Molecular Biology Techniques; Optics; Organic Synthesis; Pathway interactions; Patients; Peptide Synthesis; Peptides; Peripheral; Photons; Positron-Emission Tomography; Process; Property; Quality of life; Scheme; Screening for cancer; Series; Signal Transduction; Solutions; Staging; Structure; Structure-Activity Relationship; Survival Rate; Techniques; Testing; Tissues; Toxic effect; Training; Tumor Cell Line; Validation; Width; X-Ray Computed Tomography; absorption; base; biomaterial compatibility; cancer diagnosis; chromophore; combinatorial; design; fight against; fluorophore; functional group; improved; in vivo; luminescence; optical imaging; practical application; prevent; prospective; public health relevance; quantum; tumor; tumor specificity; two-photon; uptake; vector

DESCRIPTION (provided by applicant): Early detection of cancer is essential to improve patient's survival rates and quality of life. Near-infrared (NIR) optical imaging using a NIR fluorescent contrast agent is one relatively undeveloped modality for tumor detection whose potential has not yet been fully realized. Lanthanide ions (Ln3+) have luminescent properties well suited for application as NIR contrast agents and one promising platform for sensitization of Ln3+ ions for NIR fluorescence is a class of supramolecular structures called metallacrowns (MC). The focus of this proposal will be to synthesize and develop Ln3+[MC] complexes for tumor imaging applications. Specifically we will 1) synthesize a series of Ln3+[MC] structures and characterize their photophysical properties in order to determine the energy transfer mechanism, 2) design new MC ligands to absorb in the visible region while attaching peptide translocation vectors, and 3) assess in vitro biocompatibility against a range of tumor cell lines. Using the series of Ln3+[MC] structures that have been synthesized to date, key photophysical parameters, such as emission wavelength (?f), fluorescence quantum yield (?f), fluorescence lifetime (¿f), and hydration number (q), will be tabulated providing the necessary information for further synthetic refinement and optimization of NIR fluorescence. Deuterated ligands will be explored to determine which parts of the molecule participate in energy transfer to the Ln3+ ion. New ligands based on fluorone dyes will also be made to further shift the absorption into the visible. These new ligands will allow introduction of functional groups for conjugation to tumor targeting peptides which will be synthesized de novo. Finally, Ln3+[MC]s with the most promising optical properties and those conjugated to tumor targeting peptides will be advanced to in vitro studies of biocompatibility that will include examination of solution stability, cell viability, celular uptake, and intracellular fluorescence. Overall, this synthetic strategy followed by preliminary biological assessment will inform further synthetic refinement. Completion of these studies will provide a better understanding of the fluorescent properties of Ln3+[MC]s and identify promising candidates for practical application as NIR fluorescent tumor contrast agents.

描述（通过应用提供）：癌症的早期发现对于提高患者的存活率和生活质量至关重要。使用NIR荧光对比剂的近红外（NIR）光学成像是一种相对未开发的肿瘤检测方式，其潜力尚未完全实现。 Lanthanide离子（LN3+）具有非常适合用作NIR对比剂的发光特性，而LN3+离子对NIR荧光的敏感性的一个有望平台是一类称为Metallacrowns（MC）的超分子结构。该提案的重点是合成和开发用于肿瘤成像应用的LN3+[MC]复合物。具体而言，我们将1）合成一系列LN3+[MC]结构并表征其光物理特性，以确定能量传递机制，2）设计新的MC配体以吸收可见的区域，同时连接肽易位载体，而3）评估体外生物兼容性范围内的肿瘤细胞系列。使用迄今已合成的一系列LN3+[MC]结构，关键的光物理参数，例如发射波长（？f），荧光量子产率（？f），荧光寿命（F）和水合数（Q），将为进一步的综合细化和优化的nirir luretlistence提供必要的信息（Q）。将探索深思配体，以确定分子参与能量转移到LN3+离子的哪些部分。还将制作基于氟元染料的新配体，以将抽象进一步转移到可见度中。这些新的配体将允许引入官能团，以将靶向肽的肿瘤结合起来，这将是从头合成的。最后，具有最有前途的光学特性的LN3+[MC]，与靶向Petides的肿瘤相结合的LN3+[MC]将进行生物相容性的体外研究，其中包括检查溶液稳定性，细胞活力，细胞摄取和细胞内荧光。总体而言，这种综合策略遵循初步的生物学评估将为进一步的合成精致提供信息。这些研究的完成将更好地理解LN3+[MC] S的荧光性能，并确定实际应用的承诺候选物作为NIR荧光肿瘤对比剂。