CAREER: Engineering Tunable Fluorescent Organic Salts for Next Generation Imaging and Photodynamic Therapy

这个项目将使用荧光有机盐来提供一种在细胞水平上控制光激发(即光激活)相互作用的新方法。首席研究人员致力于改进荧光染料，以限制应用于细胞成像和光动力疗法(PDT)的毒性。该方法将开发一系列有机盐，评估光毒性(即光毒性)，然后评估所选的造影剂。改进后的显像剂将得到广泛应用，初步数据表明，光毒性有所降低。这项研究可以导致新的荧光探针，从生物医学和诊断到太阳能电池，通过实现没有副作用的选择性光动力学疗法；更明亮的医学成像，更深入组织的肿瘤检测和图像引导手术。主要研究人员利用一种新的方法，将荧光离子与非荧光反离子配对，独立调节前沿分子轨道水平，建议对细胞和光毒性负责，而不改变光学性质。首席研究人员提出，微调概念既可以应用于新型的荧光探针，也可以应用于商业上可获得的荧光探针，并将使荧光探针在真核细胞中的一系列应用能够精确地调节毒性。首席研究员将系统地设计一系列离子，通过调节卤化程度、空间体积和偶极矩来调节荧光有机盐的光电性质。中心假设将测试荧光有机盐是否通过反离子耦合在细胞环境中通过电荷注入产生共振的活性氧物种来提供细胞毒性和光毒性可调性。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This project will use fluorescent organic salts to provide a new way for controlling photoexcited (i.e., activated by light) interactions at the cellular level. The principal investigator seeks to improve fluorescent dyes to limit toxicity for application to cell imaging and photodynamic therapy (PDT). The approach will develop a range of organic salts, assess phototoxicity (i.e., toxicity due to light) and then evaluate the chosen contrast agents. Improved imaging agents will be broadly useful and preliminary data suggest a reduction in phototoxicity. The research can lead to novel fluorescent probes for broad societal impact ranging from biomedicine and diagnostics to solar cells by enabling selective photodynamic therapy without side effects; brighter medical imaging that penetrate deeper into tissue for tumor detection and image-guided surgery.The principal investigator utilizes a new approach that will pair fluorescent ions with non-fluorescent counterions to independently modulate frontier molecular orbital levels proposed to be responsible for cyto- and photo-toxicity, without modifying optical properties. The principal investigator proposes that the fine-tuning concept can be applied to both novel and commercially available fluorescent probes and will enable precise toxicity modulation of fluorescent probes in eukaryotic cells for a range of applications. The principal investigator will systematically engineer a series of ions that tune optoelectronic properties of fluorescent organic salts by modulating the degree of halogenation, steric bulk, and dipole moments. The central hypothesis will test if fluorescent organic salts provide cytotoxic and phototoxic tunability through counterion coupling by generating resonant reactive oxygen species via charge injection in cellular environments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.