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Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu\u2010FP). PG@Cu\u2010FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol\u2010based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu\u2010FP successfully reduces the activation of the nucleotide\u2010binding oligomerization domain\u2010like receptor family pyrin domain\u2010containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod\u2010like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu\u2010FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu\u2010FP in improving IVDD and provide novel insights for future research in IVDD treatments.<\/jats:p>","DOI":"10.1002\/smll.202308167","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:44:40Z","timestamp":1699843480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Enhanced Mitochondrial Targeting and Inhibition of Pyroptosis with Multifunctional Metallopolyphenol Nanoparticles in Intervertebral Disc Degeneration"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2872-7097","authenticated-orcid":false,"given":"Hao","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Key Laboratory of Structural Malformations in Children of Zhejiang Province Key Laboratory of Orthopaedics of Zhejiang Province The Second Affiliated Hospital and Yuying Children's Hospital of 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