State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
Department of Biomedical Engineering/Computer Application, Fourth Military Medical University, Xi'an 710032, China.
Biosensors (Basel). 2022 Jul 24;12(8):558. doi: 10.3390/bios12080558.
Tumor accurate imaging can effectively guide tumor resection and accurate follow-up targeted therapy. The development of imaging-stable, safe, and metabolizable contrast agents is key to accurate tumor imaging. Herein, ultra-small and metabolizable dual-mode imaging probe Au/Gd@FA NCs is rationally engineered by a simple hydrothermal method to achieve accurate FL/MRI imaging of tumors. The probes exhibit ultra-small size (2.5-3.0 nm), near-infrared fluorescence (690 nm), high quantum yield (4.4%), and a better T nuclear magnetic signal compared to commercial MRI contrast agents. By modifying the folic acid (FA) molecules, the uptake and targeting of the probes are effectively improved, enabling specific fluorescence imaging of breast cancer. Au/Gd@FA NCs with good biosafety were found to be excreted in the feces after imaging without affecting the normal physiological metabolism of mice. Intracellular reactive oxygen species (ROS) increased significantly after incubation of Au/Gd@FA NCs with tumor cells under 660 nm laser irradiation, indicating that Au/Gd@FA NCs can promote intracellular ROS production and effectively induce cell apoptosis. Thus, metabolizable Au/Gd@FA NCs provide a potential candidate probe for multimodal imaging and tumor diagnosis in clinical basic research. Meanwhile, Au/Gd@FA NCs mediated excessive intracellular production of ROS that could help promote tumor cell death.
肿瘤精准成像可以有效指导肿瘤切除和精准的靶向治疗。开发成像稳定、安全、可代谢的对比剂是实现精准肿瘤成像的关键。在此,通过一种简单的水热法合理设计了超小且可代谢的双模成像探针 Au/Gd@FA NCs,以实现肿瘤的准确荧光/MRI 成像。该探针具有超小尺寸(2.5-3.0nm)、近红外荧光(690nm)、高量子产率(4.4%)和优于商业 MRI 造影剂的 T1 核磁共振信号。通过修饰叶酸(FA)分子,有效提高了探针的摄取和靶向性,能够特异性地对乳腺癌进行荧光成像。成像后,具有良好生物安全性的 Au/Gd@FA NCs 被发现以粪便形式排出,而不影响小鼠的正常生理代谢。在 660nm 激光照射下,Au/Gd@FA NCs 与肿瘤细胞孵育后,细胞内活性氧(ROS)显著增加,表明 Au/Gd@FA NCs 可以促进细胞内 ROS 的产生,并有效诱导细胞凋亡。因此,可代谢的 Au/Gd@FA NCs 为临床基础研究中的多模态成像和肿瘤诊断提供了一种潜在的候选探针。同时,Au/Gd@FA NCs 介导的细胞内过量 ROS 产生有助于促进肿瘤细胞死亡。