生物正交点击反应增强自然杀伤细胞对肿瘤识别的可设计纳米适配器数据集
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针对免疫细胞对肿瘤细胞的识别效率较低的难题。我们提出了一种基于生物正交反应的功能化纳米适配器设计策略,用于增强免疫细胞对体内肿瘤细胞的靶向识别。这一策略通过两个过程实现:1)在肿瘤细胞表面构建多价化学受体,源于纳米适配器的高效的肿瘤靶向能力,导致“一对多”化学受体谱的构建;2)生物正交点击反应介导预处理免疫细胞对体内肿瘤细胞的多价识别。作为概念验证(图1),我们使用透明质酸(HA)和二苯并环辛炔(DBCO)功能化Au:Ag2Te近红外二区荧光量子点,以形成可连接肿瘤细胞和免疫细胞的纳米适配器(HA/DBCO-Au:Ag2Te,Nano-adaptor)。在纳米适配器中,HA作为靶向配体分子用于特异性结合CD44,CD44是人肺癌A549肿瘤细胞的典型膜标志物。DBCO作为肿瘤细胞表面上的化学受体用于体内捕获AgAuSe荧光量子点标记的叠氮化物工程化的NK细胞(NIR-II-NK92-N3),利用高度特异性点击反应和多价结合效应,在活体水平介导过继性NK92细胞对肿瘤高效识别。同时,利用多通路动态近红外二区荧光成像技术对纳米适配器进行原位实时跟踪监测(λem = 1607 nm)和NIR-II的NK92-N3(λem = 1050 nm)。综上,所制备的纳米适配器不仅表现出精确的肿瘤靶向能力,而且还有效地介导肿瘤部位的NK92细胞富集。这种新型策略在免疫细胞的肿瘤治疗应用中具有广阔的前景
To address the challenge of low recognition efficiency of immune cells against tumor cells, we propose a design strategy for functionalized nano-adaptors based on bioorthogonal reactions to enhance the targeted recognition of tumor cells in vivo by immune cells. This strategy is realized through two processes: 1) Construction of multivalent chemical receptors on the surface of tumor cells: derived from the excellent tumor-targeting capability of nano-adaptors, a "one-to-many" chemical receptor profile is established; 2) Multivalent recognition of tumor cells in vivo by pretreated immune cells mediated via bioorthogonal click reactions. As a proof-of-concept (Figure 1), we functionalized Au:Ag2Te second near-infrared window (NIR-II) fluorescent quantum dots with hyaluronic acid (HA) and dibenzocyclooctyne (DBCO) to form nano-adaptors (HA/DBCO-Au:Ag2Te, Nano-adaptor) that can link tumor cells and immune cells. In this nano-adaptor, HA acts as a targeting ligand to specifically bind to CD44, a typical membrane marker of human lung cancer A549 tumor cells. DBCO serves as chemical receptors on the surface of tumor cells to capture azide-engineered NK92 cells labeled with AgAuSe NIR-II fluorescent quantum dots (NIR-II-NK92-N3). By leveraging the highly specific click reaction and multivalent binding effect, this system mediates efficient recognition of tumor cells by adoptively transferred NK92 cells in vivo. Meanwhile, multiplex dynamic NIR-II fluorescence imaging technology is used to perform in situ real-time tracking and monitoring of the nano-adaptors (λem = 1607 nm) and NIR-II-NK92-N3 cells (λem = 1050 nm). In summary, the prepared nano-adaptors not only exhibit precise tumor-targeting capability, but also effectively mediate the enrichment of NK92 cells at tumor sites. This novel strategy holds broad prospects for applications in immune cell-mediated tumor therapy.




