CAS Center for Excellence in Nanoscience, Institute of Intelligent Machines, Chinese Academy of Sciences , Hefei, Anhui 230031, China.
Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, China.
ACS Appl Mater Interfaces. 2017 Nov 8;9(44):38222-38229. doi: 10.1021/acsami.7b10409. Epub 2017 Oct 25.
Precise identification and detection of cancer cells using nanoparticle probes are critically important for early cancer diagnosis and subsequent therapy. We herein develop novel folate receptor (FR)-targeted surface-enhanced Raman scattering (SERS) nanoprobes for cancer cell imaging based on a click coupling strategy. A Raman-active derivative (5,5'-dithiobis(2-nitrobenzoic acid)-N (DNBA-N)) is designed with a disulfide bond for covalently anchoring to the surface of hollow gold nanoparticles (HAuNPs) and a terminal azide group for facilitating highly efficient conjugation with the bioligand. Modification of HAuNPs with DNBA-N yields monolayer coverage of Raman labels absorbed on the nanoparticle surface (HAuNP-DNBA-N) and strong SERS signals. HAuNP-DNBA-N can be simply and effectively conjugated with folate bicyclo[6.1.0]nonyne derivatives via a copper-free click reaction. The synthesized nanoprobes (HAuNP-DNBA-folic acid (FA)) exhibit excellent targeted capacities to FR-positive cancer cells relative to FR-negative cells through SERS mappings. The receptor-mediated delivery behaviors are confirmed by comparison with the uptake of HAuNP-DNBA-N and free FA competition experiments. In addition to its good stability and benign biocompatibility, the developed SERS nanoprobes have great potential for applications in targeted tumor imaging.
使用纳米颗粒探针精确识别和检测癌细胞对于早期癌症诊断和后续治疗至关重要。我们在此基于点击偶联策略开发了用于癌细胞成像的新型叶酸受体(FR)靶向表面增强拉曼散射(SERS)纳米探针。设计了一种具有二硫键的拉曼活性衍生物(5,5'-二硫代双(2-硝基苯甲酸)-N(DNBA-N)),用于共价固定在中空金纳米颗粒(HAuNPs)的表面,并带有末端叠氮基团,以促进与生物配体的高效偶联。DNBA-N 对 HAuNPs 的修饰产生了拉曼标记物单层覆盖物,这些标记物被吸收在纳米颗粒表面(HAuNP-DNBA-N)上,从而产生强 SERS 信号。通过无铜点击反应,HAuNP-DNBA-N 可以简单有效地与叶酸二环[6.1.0]壬炔衍生物偶联。与 FR 阴性细胞相比,合成的纳米探针(HAuNP-DNBA-叶酸(FA))通过 SERS 图谱显示出对 FR 阳性癌细胞具有优异的靶向能力。通过与 HAuNP-DNBA-N 的摄取和游离 FA 竞争实验的比较,证实了受体介导的递药行为。除了良好的稳定性和良性生物相容性外,所开发的 SERS 纳米探针在靶向肿瘤成像方面具有很大的应用潜力。
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