双重富集增敏型近红外Ag2S量子点的构建及其肿瘤光学诊疗研究

Small-sized Ag2S quantum dots (QDs) that integrates three functions of NIR-II fluorescence imaging, photoacoustic imaging, and photothermal therapy have shown great advantages and potential in tumor imaging and therapy. However, small Ag2S QDs could re-enter the bloodstream or move to the surrounding normal tissues, resulting in the depletion of Ag2S QDs amount retained within tumors and the loss of optical imaging sensitivity and photothermal efficacy. In this project, we will construct dual-accumulated near-infrared Ag2S QDs by connecting the targeting ligand-iRGD peptide to thermosensitive polymer on the surface of Ag2S QDs via acid-sensitive chemical bond. Based on the complementary advantages of active targeting and acidic tumor microenvironment triggered aggregation, Ag2S QDs could effectively locate to and then retain in the tumor to realize enhanced tumor accumulation. Finally, dual-accumulated near-infrared Ag2S QDs will be applied to NIR-II fluorescence/photoacoustic dual-modal imaging and photothermal therapy of tumor. The enhancement effect of tumor dual accumulation on optical imaging sensitivity and photothermal efficacy of Ag2S QDs will also be evaluated. This project will offer a new perspective to construct high-performance theranostic nanoplatforms, and contribute to the development of novel highly effective tumor theranostic techniques.

小粒径Ag2S量子点（QDs）集近红外二区荧光成像、光声成像和光热治疗三种功能于一体，在活体肿瘤成像与治疗研究中表现出巨大的优势和潜力。然而，它们在到达肿瘤组织后，易回流到血液中或转移到周边正常组织，导致其肿瘤富集效率降低，从而影响其光学成像灵敏度和光热疗效。为此，本项目拟将温敏聚合物修饰到Ag2S QDs表面，并通过酸敏感键与靶向配体iRGD肽连接，构建双重富集增敏型近红外Ag2S QDs。通过主动靶向和肿瘤酸性微环境响应性聚集的优势互补，促使Ag2S QDs高效到达并有效滞留在肿瘤组织，从而极大地提升其在肿瘤组织中的富集效率。进而开展基于该Ag2S QDs的活体肿瘤近红外二区荧光/光声双模态成像和光热治疗研究，评价肿瘤双重富集策略对Ag2S QDs光学成像灵敏度和光热疗效的增强效应。本项目为构建高性能肿瘤诊疗剂提供了新思路，为发展新型高效的肿瘤诊断和治疗技术奠定基础。

小粒径Ag2S量子点（QDs）在到达肿瘤组织后，易回流到血液中或转移到周边正常组织，导致其肿瘤富集效率降低，从而影响其光学成像灵敏度和光热疗效。本项目以构建高效肿瘤诊疗探针为目的，主要从以下两方面开展相关研究。首先，设计并合成了粒径较小的共聚物纳米颗粒，可以将化疗药物阿霉素（DOX）递送至实体瘤深处，并能在肿瘤细胞内高浓度谷胱甘肽（GSH）条件下快速释放DOX至细胞核内，实现对实体瘤的高效抑制。充分证实了小粒径纳米材料具有深的肿瘤组织穿透性。进一步地，利用肿瘤微环境刺激响应性聚集策略，来提升小粒径Ag2S QDs在肿瘤组织中的富集效率。将合成的酸敏感型或还原敏感型两亲性聚合物修饰到Ag2S QDs表面，制备两种智能型Ag2S QDs。到达肿瘤组织后，在微酸环境或高浓度GSH刺激下，Ag2S QDs的表面结构发生改变，导致其发生原位聚集。通过优化聚合物的分子结构来调控Ag2S QDs的聚集行为，探究了Ag2S QDs发生聚集后的光学性能，最终实现活体肿瘤的高灵敏度成像和高效光热治疗。本项目的顺利完成为构建智能响应型肿瘤诊疗探针提供了新思路，为发展新型高效的肿瘤诊断和治疗技术奠定基础。