Stem Cell Membrane-Camouflaged\nBiomimetic Nanoparticles\nInhibiting Leptin Pathway for Intervertebral Disc Degeneration Therapy

Leptin, a kind of adipokine, with its receptor in which\nthe long\nisoform plays a crucial role in signal transduction, has been identified\nin intervertebral disc (IVD) tissues, especially showing an increased\nexpression in degenerated discs. Initially identified as a metabolic\nsensor, leptin has recently been found able to regulate inflammation\ninto imbalance, which favors catabolic degradative processes, thus\ncontributing to progressive intervertebral disc degeneration (IDD).\nTherefore, efficiently inhibiting the leptin pathway may provide a\nnew strategy to treat IDD. In this study, we introduced an innovative\ndrug delivery system (DDS) that employs stem cell membranes (SCM)\nto encapsulate (Zeolitic imidazolate frameworks-8) ZIF-8 nanoparticles.\nThese nanoparticles are used to transport a plasmid containing shRNA\ntargeting the leptin receptor (LEPR), with the aim of facilitating\nrepair in IDD. The regenerative performances of this DDS in IDD were\nverified through a combination of the <i>in vitro</i> western\nblot and immunofluorescence with the <i>in vivo</i> radiologic\nexamination and histological staining. The DDS demonstrated excellent\ncell adhesion properties and gene transfection efficiency <i>in vitro</i>, along with impressive treatment outcomes <i>in vivo</i>. Both <i>in vitro</i> and <i>in vivo</i> studies revealed that the DDS effectively reduced leptin receptor\nexpression and alleviated the inflammatory environment, thereby promoting\nregeneration in degenerated IVDs. We propose that the DDS represents\na promising novel approach for treating IDD and may also be beneficial\nfor other degenerative diseases linked to leptin pathway dysfunction.