NIR-II Imaging Guided Accurate Identification of Paraspinal Muscle Degeneration Through Targeting the Lysosomal Membrane Protein Sidt2.

Abstract

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.