Guanghao Piao,1,2,* Limin Fan,3,* Yanmin Zhang,4,5,* Wen Jiang,5 Xiaoping Guo,4 Rui Liu,1 Qian Wang,6 Sihan Jia,6 Junqin Liang,6,7 Yizhou Li1,6,7 

1Department of Orthopedics, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010000, People’s Republic of China; 2Department of Orthopedics, Baogang Hospital of Inner Mongolia, Baotou, 014010, People’s Republic of China; 3School of Medicine, Tongji University, Shanghai, 200000, People’s Republic of China; 4Otolaryngology Diagnosis and Treatment Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, People’s Republic of China; 5Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, People’s Republic of China; 6Department of Allergy, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, People’s Republic of China; 7Treatment Center of Biomedicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830001, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Junqin Liang, Email gyx19960122@163.com Yizhou Li, Email yzliyizhou@163.com

Background: This study introduces a novel imaging approach for early detection of degenerative paraspinal muscle disorders, which are a key contributor to lower back pain and lumbar-related diseases. The core concept involves the use of a lanthanide-doped nanoprobe with a core@shell structure (NaYbF₄:x%Er@NaYF₄:x%Yb@NaYF₄), designed to function as a second near-infrared (NIR-II) fluorescent probe. This probe demonstrates significant advantages such as deep tissue penetration, high spatial and temporal resolution, and exceptional stability, enabling in vivo monitoring of muscle degeneration.
Methods: To achieve precise imaging of degenerative paraspinal muscles, a core@shell structure lanthanide nanoprobe of NaYbF4:x%Er@NaYF4:x%Yb @NaYF4 was designed through adjusting the lanthanide concentration parameters and outer shell structure thickness in the probe structure so that these adjustments improved its fluorescence efficiency and long fluorescence life. Based on the results of mRNA sequencing, our findings support Sidt2 as a reliable and potentially specific marker for paraspinal muscle degeneration. The fluorescent probe was functionalized with an antibody specifically targeting the upregulated lysosomal membrane protein Sidt2.
Results: Notably, in a mice model of degenerative paraspinal muscles, the Sidt2-targeted nanoprobe selectively accumulated in the degenerative muscle tissues, displaying intense fluorescence signals. Fluorescence intensity measurements from the region of interest (ROI) in the degenerated paraspinal muscle showed NIR-II intensities of up to 200 a.u. with consistent fluorescence for 8 hours post-injection. Biological assays demonstrated a strong correlation between fluorescence intensity and the extent of muscle degeneration.
Conclusion: This study presents a platform for ultra-early detection of degenerative paraspinal muscles using NIR-II imaging, providing a theoretical basis for early intervention based on the multifunctionality of nanoprobes. This is the first application of NIR-II fluorescence imaging to assess muscle tissue lesions, and the results strongly support advancing to the next phase, which involves using multifunctional probe technology to intervene in paraspinal muscle degeneration.

Keywords: Sidt2, paraspinal muscle degeneration, NIR-II fluorescence imaging, lanthanide nanoprobe