Chemistry of multimodal imaging tools for image guided surgery in glioblastoma

该项目旨在利用生物共轭的量子点来特异性靶向胶质母细胞瘤肿瘤和实时荧光成像;这可能适用于帮助外科医生进行术中肿瘤切除。此外，将研究量子点作为胶质母细胞瘤术前成像（例如MRI/PET）的多模态成像工具的潜在用途。在本项目中，InP/ZnS核/壳量子点和Ag基量子点的合成将使用最近建立的用于可见光和近红外区域荧光发射的方法进行。将利用有机方法来合成用于特异性靶向胶质母细胞瘤的生物学相关分子，例如当PSMA在胶质母细胞瘤中过表达时，可以利用基于PSMA-11的PSMA靶向基序来缀合至量子点。也可以使用胶质母细胞瘤的其他已建立的靶标，例如抗体和其他基于短肽的药物。量子点与特异性结合分子的官能化是通过基于PEG的接头，并最终在量子点的表面上掺入基于Gd的络合物和Ga-68。在项目中定期对制备的化合物进行表征。量子点通过UV-Vis，DLS和荧光进行表征;合成的分子通过TLC，NMR，LCMS，IR和元素分析进行表征。将通过流式细胞术和基于显微镜的方法在胶质母细胞瘤细胞系（例如U87 MG细胞）中进行评价。对于MRI等术前方法，将使用NMR扫描仪发现材料的弛豫率并用于获得图像。根据成胶质细胞瘤细胞中成功的特异性摄取，可以在成胶质细胞瘤小鼠模型上进行临床前实验。

This project aims to utilise quantum dots that are bioconjugated to specifically target glioblastoma tumours and real-time fluorescence imaging; this may be applied to aid surgeons in intraoperative tumour resections. Furthermore, the potential use of quantum dots as multimodal imaging tools for preoperative imaging (e.g. MRI/PET) of glioblastoma will be studied. In this project, synthesis of InP/ZnS core/shell quantum dots and Ag-based quantum dots will be carried out using recently established methods for fluorescence emission in visible and near infrared regions. Organic methods will be utilised to synthesise biologically relevant molecules for specific targeting of glioblastoma e.g. as PSMA is overexpressed in glioblastoma a PSMA-targeting motif based on PSMA-11 may be utilised to conjugate to the quantum dot. Other established targets for glioblastoma may also be used e.g. antibodies and other short peptide based drugs. Functionalisation of the quantum dot with the specifically binding molecule is through a PEG based linker and eventually incorporation of Gd-based complexes and Ga-68 on the surface of the quantum dot. Characterisation of prepared compounds is carried out regularly in the project. Quantum dots are characterised through UV-Vis, DLS and fluorescence; synthesised molecules are characterised through TLC, NMR, LCMS, IR and elemental analysis. Evaluation will be carried out in glioblastoma cell lines (e.g. U87MG cells) through flow cytometry and microscopy based methods. For preoperative methods such as MRI, the relaxivity of the material will be found with the use of NMR scanners and used to obtain images. Dependent on the successful specific uptake in glioblastoma cells, preclinical experiments may be carried out on glioblastoma mouse models.