基于99mTc标记两亲性染料自组装纳米颗粒的FUCL/PA/SPECT三模态成像造影剂的开发及其肿瘤诊疗的研究

分子影像学的发展对肿瘤的早期诊断和精准治疗具有十分重要的意义。为了整合不同的分子影像技术在灵敏度、空间分辨率和成像深度等的优势，本课题开发了一系列99mTc标记的两亲性近红外染料自组装的纳米探针。此纳米探针内核为具有频率上转换发光(FUCL)和光声(PA)功能的疏水性近红外染料，中间层是亲水性高分子PEG，表面标记了可用于单光子发射计算机断层成像(SPECT)的核素99mTc，其可在细胞、组织和活体多个层次上实现对肿瘤进行三模态靶向成像。同时，基于两亲性染料自组装的原理，我们设计的纳米探针为放疗剂、化疗剂、光热剂和光动力疗剂等多种治疗试剂提供了优良的纳米载体，有望为肿瘤的多模态早期诊断和精准治疗提供有利的帮助。

The developments of the molecular imaging play a significant role in diagnostic imaging and therapeutic treatment of early tumor. To improve effectively the sensitivity, spatial resolution and imaging depth of different molecular imaging, we developed a series of 99mTc-labeled nanoprobes based on the self-assembly of amphipathic near-infrared (NIR) dyes. The core NIR dyes of nanoprobes showed good frequency upconversion luminescence (FUCL) and photoacoustic (PA) signals, and the surface 99mTc could be labeled for single-photon emission computed tomography (SPECT). The nanoprobes were successfully used in FUCL/PA/SPECT multimodality imaging for tumor in vitro and in vivo. Meanwhile, based on the concept of self-assembly of amphipathic dyes, the nanoprobes support an important nanoplatform for the multi-treatment of tumor, such as radiotherapy, chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT) etc. Herein, the nanoprobe developed integrate multi-functionality in one nanoplatform for enabling early diagnostic imaging of tumor and imaging guided therapy.