高效光子上转换纳米粒子及其与耦联生物分子相互作用的调控研究

To obtain high biological compatibility of photon conversion nanoparticles (UNs) and high biosensitivity and biospecificity of anti-body coupled with Uns, is a key or premising of applications of UNs for many fields such as biomarkers and medical photonic imaging. In this project, these technologies are going to be used for surface biomodification methods in which UNs are couplied with protein G which can control the target spot and direction of anti-body molecules coupled with protein on the UNs, in which the stronger interactions between UNs and anti-body due to no rigid coupling between UNs and anti-body molecules. The conditions and law of the coupling anti-body with UNs will be studied, including the interactions between the UNs and anti-body, the protein and anti-body, and anti-body and antigen molecules, to solve the difficulties with low bio-sensitivity and bio-specificity of anti-body coupled directly with UNs, and to offer physical basis for applications of high properties of UNs-protein-antibody as novel UNs, which is of important significance in many fields for research and application

获得高生物相容性光子上转换纳米粒子（UNs）及其与抗体高性能偶联的光子上转换高靶向灵敏性和特异性是实现UNPs生物标记和医学光子成像应用的前提和关键。本课题应用小蛋白分子对UNs表面进行特种修饰，实现UNs与抗体间非刚性偶联、与单抗非易变片段区的选择性偶联而非与易变区偶联,提高与UNs偶联单抗的免疫活性、生物灵敏性和特异性。研究UNs与抗体之间进行取向和位点可控地非刚性偶联的最佳条件和规律。研究UNs与蛋白G的表面与界面、蛋白G与单抗分子的表面与界面、UNs与抗体的表面与界面之间相互作用以及UNs生物标记和生物成效的功效。为解决和提高所有与纳米材料（包括所有载体）偶联生物分子的免疫活性、结合灵敏性和特异性低的难题，提供物理基础和依据。对解决具有纳米生物材料或器件的免疫活性、生物灵敏性和特异性差的领域性难题具有普适性的实际意义。

针对获得光子上转换纳米粒子（UCNPs）及其与抗体偶联的高特异性生物探针的关键问题， 开展了：1）高效发光及生物相容性的UNs探针制备研究；2）高效UNs与各种分子如有机近红外分子、生物光敏剂分子相互作用机制的物理图像研究，着重构建其偶联动力学发光传递过程物理图像；3）通过研究UCNPs与抗体分子相互作用，在固相基底上高效富集与抗体结合的UCNPs，构建出UCNPs检测抗原的高灵敏检测探针，实现固相基底基的高灵敏和高特异性的抗原检测；4）通过蛋白G为“桥”，实现了UCNPs与抗体的生物“柔性”耦联，并利用UCNPs可近红外光激发和发射优势，实现了微量全血检测的高特异性和高灵敏度（1.82 nmol /L）。本项目的研究工作对解决具有纳米生物材料或器件的免疫活性、生物灵敏性和特异性差的领域性难题具有普适性的实际意义。本项目发表SCI论文11篇，申请专利6项，培养博士生3人，硕士2人。