Biophotonics: Biospecific Contrast Agents for Pre-Cancer Detection

该提案汇集了来自不同领域的科学家，目标是开发新的光子探针和造影剂，用于高灵敏度和选择性地检测体内的癌前病变。Andrew Ellington博士将使用组合化学的方法开发一个适配体分子文库，该文库针对宫颈癌和癌前细胞表面的生物分子靶点。他将使用Lotan博士提供的处于癌症发展不同阶段的成熟的宫颈细胞系。Drs。Brian Korgel和Konstantin Sokolov将开发基于量子点（BK）和金属纳米粒子（KS）的新型光子探针。他们将利用艾灵顿博士开发的适体以及目前在临床组织病理学中使用的知名抗体。Rebecca Richards- Kortum博士将使用光学显微镜和光谱学对这些偶联物作为分子特异性造影剂进行测试。她将使用Lotan博士提供的宫颈癌细胞系，三维组织模型和Follen博士提供的新鲜宫颈组织切片。在不同复杂程度下，对代表正常和肿瘤子宫颈特性的所有三种生物系统进行实验，将用于评估和改进新造影剂的性能和检测方案。这种改进将包括制备对癌症特定靶点具有高亲和力的生物工程适体，定制金属纳米颗粒和量子点的光学特性，优化共轭程序，以及开发最佳成像几何形状。

0119450 Richards-Kortum This proposal brings together scientists from very diverse areas with the goal of developing new photonic probes and contrast agents for highly sensitive and selective detection of pre-cancers in vivo . Dr. Andrew Ellington will use the approaches of combinatorial chemistry to develop a library of aptamer molecules specific for biomolecular targets on the surface of cervical cancerous and pre-cancerous cells. He will use well-established cervical cell lines at different stages of cancer development provided by Dr. Lotan. Drs. Brian Korgel and Konstantin Sokolov will develop new photonic probes based on quantum dots (BK) and metal nanoparticles (KS). They will utilize both the aptamers developed by Dr. Ellington as well as well-known antibodies currently used in clinical histopathology. Dr. Rebecca Richards- Kortum will test the conjugates as molecular specific contrast agents using optical microscopy and spectroscopy. She will use cervical cancer cell lines provided by Dr. Lotan, three-dimensional tissue phantoms and fresh cervical tissue slices from Dr. Follen. Experiments with all three biological systems representing properties of normal and neoplastic cervix at different levels of complexity will be used to assess and refine the performance and detection scheme for the new contrast agents. This refinement will include preparing bioengineered aptamers with high affinity to cancer specific targets, tailoring optical properties of metal nanoparticles and quantum dots, optimizing conjugation procedures, and developing optimal imaging geometries.