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Here, we found that senescent nucleus pulposus (NP) cells accumulated and released double\u2010stranded DNA (dsDNA), which reinforced NP cell senescence and matrix catabolism. The accumulated dsDNA also activated cGAS\u2013STING signaling, increased Netrin\u20101 expression, and promoted neuronal migration and neurite outgrowth. Guided by these findings, we developed RU@PEI\u2010ZIF, a dual\u2010functional nanoplatform combining PEI\u2010mediated dsDNA scavenging with ZIF\u20108\u2010mediated delivery of the cGAS inhibitor RU.521. RU@PEI\u2010ZIF displayed dsDNA\u2010binding capacity, cytocompatibility, and pH\u2010responsive RU.521 release. In senescent NP cells, RU@PEI\u2010ZIF reduced extracellular and cytosolic dsDNA, attenuated cGAS\u2013STING\u2010associated inflammatory and neurotrophic signaling, and reduced NP cell\u2010mediated neuronal migration and neurite outgrowth. In an animal model of disc degeneration, intradiscal RU@PEI\u2010ZIF reduced disc degeneration, NP cell senescence, pathological sensory innervation, and pain hypersensitivity. These findings support RU@PEI\u2010ZIF as a dual\u2010action nanotherapeutic strategy targeting both disc degeneration and pathological innervation.<\/jats:p>","DOI":"10.1002\/advs.78215","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:18:09Z","timestamp":1791865089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Dual\u2010Functional Nanoplatform Targeting the dsDNA\u2013cGAS Axis to Mitigate Disc Degeneration and Aberrant Innervation"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6701-4781","authenticated-orcid":false,"given":"Zhaojun","family":"He","sequence":"first","affiliation":[{"name":"Department of Orthopedics Orthopedic Hospital of Guangdong Province Academy of Orthopedics Guangdong Province The Third Affiliated Hospital of Southern Medical University  Guangzhou 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