800 nm近红外光控镧系掺杂分子探针的上转换/NIR II双模光学成像应用于乳腺癌早诊研究

无机上转换镧系掺杂探针具有低毒、性能稳定、灵敏度高、零背景干扰、抗光漂白等优势，在生物光子、生物成像和诊疗领域具有重要影响。目前镧系掺杂光学分子探针存在着“转换效率不高、穿透性有限、长期毒性不明朗”等问题，在本项目中申请者拟从以下三个方面进行研究：（1）构造镧系-金属复合探针，用离散偶极子模拟算法指导探针的结构、形貌和尺寸，提高激发源为800 nm激光的上转换材料的发光效率。（2）探究激发源为800 nm的NIR II荧光成像，实现在单光源800 nm激光激发下的上转化可见光（灵敏度高）和NIR II荧光（穿透性深）的双模成像模式。（3）在以上研究基础上，将镧系掺杂无机内核包覆可降解外壳，探究探针在人体的流转和排泄方式，实现生物相容性好、在细胞内可降解，并担载靶向分子，评估其应用于乳腺癌早诊的准确性和灵敏度。

The inorganic lanthanide-doped up-conversion probes have some typical and obvious advantages, such as, low toxicity, stable chemical and physical properties, high sensitivity, negligible background signal, and resistance to photo-bleaching, thus have a positive impact on the biophotonic, bioimaging, and theranostic fields. However, there are still some problems to be resolved referred to lanthanide-doped optical molecular probes: low conversion efficiency, low penetrating depth, and uncertain long-term toxicity, etc. In this project, I intend to do the following work: (1) To instruct the lanthanide-gold hybrid with different structures, morphologies, and sizes guided by the discrete dipole simulation (DDA), the hybrid would have improved up-conversion luminescence efficiency under the excitation of near-infrared (NIR) laser of 800 nm. (2) To realize the up-conversion and NIR II dual-modal imaging in the single probe under single excitation of 800 nm laser, the new probe may have good sensitivity and high penetration depth. (3) To explore the inorganic core/biodegradable shell probe on basis of the hybrid above and evaluate the circulation and excretion of the final probe in vivo, the final probe should have biocompatible, biodegradable, and cancer-targeted properties in cells and tissues, and could be applied in the clinical breast cancer early-detection with high accuracy and sensitivity.