基于掺杂有机纳米粒子的新型高效发光生物荧光探针

Biological fluorescence imaging plays a critical role in the early diagnosis and treatment of diseases. As the most used materials for fluorescence imaging, the limitation of poor photostability of organic dyes and biological fluorescent protein, potential toxicity of fluorescent quantum dots, and the safety problem of carriers, hampers their development in bioimaging. In this project, we will develope high luminescent doped organic nanoparticels with excellent photo- and chemical-stability and biocompatibility as novel fluorescent probes. Meanwhile, resonance energy transfer between host and guest will be utilized to help tune the emission wavelength and improve the optical quantum yield and the signal-to-noise ratio of the doped organic nanoparticles. These combined effects would make doped organic nanoparticles an excellent fluorescent probe with tunable wavelength and high brightness. Surface functionalization of doped organic nanoparticles will also be performed to achieve size- and photo-stability in different bio-environments. Biosafty will then be systematically evaluated in vitro and in vivo. Finally, the resulting functionalized organic nanoparticles will be utilized in targeted bioimaging in vitro and in vivo. This project is of great theoretical and practical significance in development of new biological fluorescence probes and applications of organic nanomaterials in biomedical field.

生物荧光成像对疾病的早期诊断与治疗具有重要意义。常用的荧光探针中，染料与生物荧光蛋白较差的抗光漂白性、荧光量子点的潜在毒性以及染料载体的生物安全性等问题都限制了其相应的发展。本项目拟发展一种高亮度且具有优异光/化学稳定性与良好生物相容性的基于掺杂有机纳米粒子的新型生物荧光探针。通过分子组装聚集形成掺杂的有机纳米粒子，利用主客体间的共振能量转移机制来调节有机纳米粒子的发光波段，同时提高其发光效率与信噪比，获得发光波段连续可调的多色优异的荧光探针。在此基础上对其进行表面功能化，实现在复杂生物环境中的尺寸及发光稳定性，系统评价其在细胞与活体层次上的生物安全性，进一步探索在细胞、活体内生物荧光成像中的应用。本课题的研究对发展新型荧光探针、拓展有机纳米材料在生物医学领域的应用，具有重要的理论和实际意义。

生物荧光成像对疾病的早期诊断与治疗具有重要意义。在本研究项目中，申请人取得了一系列创新性成果：1）在有机染料纳米颗粒的表面包裹一层薄的二氧化硅外壳，并研究染料纳米颗粒的性质对其生物荧光成像的影响，其对设计和优化成像纳米材料以用于实时示踪成像有指导意义；2）将纯药物纳米颗粒用金壳包覆后制得多功能纳米药物，其在磁靶向作用下能高效地进入肿瘤细胞，并在激光照射下实现化疗-热疗相结合的协同治疗效果；3）设计了一种线粒体靶向的双药纳米颗粒，这种纳米药物能特异性地靶向到肿瘤细胞的线粒体部位，并显著增强对肿瘤的抑制效果；4）开发了一种基于化疗药物和基因药物的组合纳米颗粒，其能够抑制小鼠肿瘤生长，并实现对肿瘤多药耐药性的有效抑制；5）设计了pH/氧化还原双重响应型双药纳米颗粒用于抗癌组合治疗，其具有高稳定性、优异的癌细胞靶向能力和可控的细胞内药物释放能力，并最终实现优于两种单独药物的抗癌效率。本课题的研究对发展新型荧光探针、拓展有机纳米材料在生物医学领域的应用，具有重要的理论和实际意义。