pH调控摄取的碘-131标记金纳米星复合材料的构建及其多模式肿瘤诊疗研究

Due to the tunable size and shape characteristics, gold nanostars demonstrate remarkable optical and photothermal properties, and can be used for CT imaging and photothermal therapy of tumor. However in biomedical applications, the amount of gold nanostars delivered to tumor site is relatively low through circulation in vivo, and it has deficiencies on imaging and therapy modes, which limit the tumor diagnostic accuracy and therapeutic efficiency of gold nanostars. Therefore, it has great research significance and application value to improve the cellular uptake of gold nanostars and build gold nanostar composites which have multimodal imaging and combination therapy functions. This project aims to utilize controlled chemical synthesis and surface modification methods to build the pH-sensitive zwitterion functionalized gold nanostar composites. According to pH-responsive charge conversion of zwitterion at tumor acidic microenvironment, the cellular uptake of gold nanostar composites in cancer cells can be improved, which enable the effective accumulation of gold nanostar composites at tumor site. After further functionalization and introducing radionuclide iodine-131, the gold nanostar composites can be constructed for SPECT/CT dual mode imaging and photothermal/radioactive combination therapy of tumor. This project will study the relationship between the structure, size, surface composition of the nanocomposites and their pH-controlled uptake property, theranostic efficiency from perspectives of molecules, cells and animals. This study will provide a new idea to explore novel and intelligent nanomaterials for multimodality theranostic of tumor.

金纳米星因可调的尺寸与形貌特征产生的光学及热学性能，可用于肿瘤CT成像和光热治疗。但在生物医学应用中，经体内循环传输至肿瘤处的金纳米星含量较低，且其成像及治疗模式存在缺陷，限制了其肿瘤诊断精确度和治疗效率。因此，提高癌细胞对金纳米星的摄取并构建兼具多模态成像和联合治疗功能的金纳米星复合材料具有重要的研究意义和应用价值。本项目拟采用可控化学合成和表面修饰等手段构建pH敏感两性离子功能化的金纳米星复合材料。根据肿瘤酸性微环境下两性离子发生pH响应电荷翻转以提升金纳米星复合材料的癌细胞摄取，实现其在肿瘤处的有效富集。进一步功能化，引入放射性核素碘-131，构建金纳米星复合材料用于肿瘤SPECT/CT双模态成像及光热/放射性联合治疗。本项目拟从分子、细胞及动物水平上研究该纳米复合材料的结构、尺寸、表面组成与其pH调控摄取性能、诊疗效率间的关系，为探索新型智能纳米材料用于肿瘤多模式诊疗提供新思路。

金纳米材料基于其较好的光学性能、X-射线衰减特性和生物相容性等，被广泛应用在生物医学领域。但由于经体内循环传输至肿瘤处的金纳米材料积累量较低，且其成像模式具有一定的局限性，导致了其肿瘤诊疗效率受限。两性离子的发展为提升金纳米材料肿瘤积累量提供了新的解决思路。本项目根据两性离子在肿瘤微酸性环境下可结合质子以实现pH响应电荷翻转，采用可控化学合成和表面修饰等方法构建pH敏感两性离子功能化的金纳米材料，并标记放射性核素锝-99m或碘-131，对构建的金纳米复合材料进行体内外SPECT/CT双模态成像评价及放射性治疗评价。从细胞和动物层面上研究了纳米复合材料的结构、组成与其成像效果、治疗效率间关系。本项目为智能纳米体系的构建及肿瘤早期精准诊疗提供了新方法。