No. 03
磁性量子点点亮创伤性脑损伤坏死神经元以解码MRI细胞来源Lighting up necrotic neurons from traumatic brain injury with magnetic quantum dots to decode the cellular origin of MRI
报道了一种锰掺杂近红外量子点，将高灵敏光学成像与临床兼容的磁共振成像内在融合，并借助全脑透明化三维成像与体外细胞实验，揭示MRI增强信号源于小胶质细胞向坏死神经元区域的趋向迁移。
创伤性脑损伤（TBI）的诊断仍严重受限于传统成像技术在可视化决定疾病进展与结局的病理事件方面的不足。为应对这一临床挑战，我们报道了一种锰掺杂近红外量子点（QD），将高灵敏光学成像与临床兼容的磁共振成像（MRI）内在地结合起来。借助全脑透明化与细胞分辨率三维（3D）全景成像所支持的光学成像，结合对TBI涉及的不同类型细胞的系统性体外细胞研究，我们通过磁性量子点的高灵敏荧光揭示了TBI成像所反映的可解释病理过程，即：经全身给药后，纳米探针经受损的血脑屏障外渗，随后被活化的小胶质细胞选择性吞噬，这些细胞继而迁移至富含死亡神经元和神经元碎片的区域。这种小胶质细胞介导的趋向性解码了纳米尺度造影剂增强MRI的信号来源，从而将MRI从解剖学工具转变为病理学报告工具。我们还将尺寸相近的生物相容性Fe 3 O 4 纳米颗粒与上述磁性量子点进行比较，以验证纳米颗粒在TBI的MRI诊断中的转化优势。
Abstract (English)
The diagnosis of traumatic brain injury (TBI) remains heavily constrained by the limitations of conventional imaging techniques in visualizing the pathological events that determine the disease progression and outcome. To address this clinical challenge, we report a manganese-doped near-infrared quantum dot (QD) to intrinsically integrate the highly sensitive optical imaging with clinical compatible magnetic resonance imaging (MRI). Taking the advantages of optical imaging powered by whole-brain clearing and cellular resolution three-dimensional (3D) panoptic imaging, in combination with the systematic in vitro cell studies on different types of cells involved in TBI, we disclosed the interpretable pathology reflected by TBI imaging through the highly sensitive fluorescence of magnetic QDs, i.e., after systemic administration, the nanoprobes were extravasated through the compromised blood-brain barrier and then selectively phagocytosed by activated microglia, which subsequently migrated into the regions rich in dead neurons and neuronal debris. This microglia-mediated tropism decodes the signal origin of MRI enhanced by the nanometer-sized contrast agent, thereby transforming the MRI from an anatomical tool into a pathological reporter. A biocompatible Fe 3 O 4 nanoparticle of similar size was also compared with the magnetic QD mentioned above for validating the translational merits of nanoparticles in MRI diagnosis of TBI.
Mingxia Jiao, Xin Zhao, Jingyun Wang, Wanru Tian, Yao Li, Xuan Cheng, Kun Zhang, Xiliang Luo, Peisen Zhang, Mingyuan Gao
Sci. Adv. 12, 45 (2026)
10.1126/sciadv.aej0686