Molecular Probes for Biomembrane Recognition

描述（由申请人提供）：有机分子探针被设计为选择性地与特定类型的生物膜结合。探针由两种结构成分组成：膜靶向配体和光活性报告基团。主要的膜靶标是人类癌细胞、垂死癌细胞和细菌的表面，其应用范围从肿瘤的体内光学成像到细菌的光学成像再到抗生素光动力治疗。主要目标是：1。开发方烷-轮烷类荧光近红外有机染料，具有前所未有的亮度和高稳定性。染料将转化为探针，用于各种类型的光学成像应用，包括对小鼠异种移植模型中生长或死亡肿瘤的成像。最终目标是检测活体动物的肿瘤或监测抗癌治疗的有效性。2. 将合成的二聚锌胺（Zn-DPA）亲和配体附着在各种荧光支架上，制备新型的细菌光学成像探针。初步结果表明，植入的小鼠细菌感染可以用发射近红外荧光的探针成像；这是活体动物体内细菌定向光学成像的第一个例子。这种新型成像方法的范围将被确定，包括对各种细菌菌株的选择性和敏感性。进一步的研究将开发高灵敏度的荧光方法，用于检测混合介质中的细菌污染，特别是生物医学样品和食品。3. 具有锌- dpa亲和配体的双功能探针将与光敏剂结合，以评估其在抗生素光动力治疗中的效用。由于锌- dpa亲和配体靶向细菌细胞膜中无处不在的极性脂质，这些双功能探针将对大多数形式的耐药细菌有效，并且用这些探针长期治疗不太可能诱导高水平的细菌耐药性。与公共卫生相关：本研究生产的荧光探针分子将用于活体动物的癌症肿瘤和细菌感染成像。成像技术将帮助研究人员发现新的治疗方法，并最终帮助医生为特定患者选择最合适的治疗方法。后一种应用是光学成像将如何促进个性化医疗概念发展的一个例子。

DESCRIPTION (provided by applicant): Organic molecular probes are designed to selectively associate with specific types of biomembranes. The probes are comprised of two structural components: a membrane targeting ligand and a photoactive reporter group. The primary membrane targets are the surfaces of human cancer cells, dying cancer cells, and bacteria, with applications ranging from in vivo optical imaging of tumors to optical imaging of bacteria to antibiotic photodynamic therapy. The major aims are: 1. Develop squaraine-rotaxanes as a new family of fluorescent near-IR organic dyes with unprecedented brightness and high stability. The dyes will be converted into probes for various types of optical imaging applications including imaging of growing or dying tumors in murine xenograft models. The eventual objective is to detect tumors in living animals or monitor the effectiveness of anticancer therapy. 2. Synthetic zinc dipicolylamine (Zn-DPA) affinity ligands will be attached to various fluorescent scaffolds to produce new optical imaging probes for bacteria. Preliminary results show that implanted murine bacterial infections can be imaged with probes that emit near-IR fluorescence; the first example of targeted optical imaging of bacteria in a living animal. The scope of this novel imaging method will be determined, including the selectivity and sensitivity for various strains of bacteria. Additional studies will develop highly sensitive fluorescent methods for detecting bacterial contamination in mixed media, especially biomedical samples and food products. 3. Bifunctional probes with Zn-DPA affinity ligands attached to a photosensitizer will be evaluated for utility in antibiotic photodynamic therapy. Since the Zn-DPA affinity ligands target ubiquitous polar lipids in the bacterial cell membrane, these bifunctional probes will be effective against most forms of drug resistant bacteria and prolonged treatment with these probes is unlikely to induce high levels of bacterial resistance. Relevance to Public Health: The fluorescent probe molecules produced by this research will be used to image cancer tumors and bacterial infection in living animals. The imaging technology will help researchers discover new therapies and eventually it will help physicians choose the most appropriate therapy for a specific patient. This latter application is an example of how optical imaging will contribute to the evolving concept of personalized medicine.