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Here, we report a temporally programmed dual\u2010module microneedles platform integrating bio\u2010inspired nanosponges (BQMNPs) as an intradermal microreservoir system with combined diagnostic and therapeutic functions. BQMNPs are constructed by encapsulating quercetin and morin within cyclodextrin nanosponges, which are subsequently incorporated into two distinct microneedle modules: polylactic\u2010co\u2010glycolic acid (PLGA)\u2010based therapeutic microneedles (T\u2010MNs) and hyaluronic acid (HA)\u2010based diagnostic microneedles (D\u2010MNs). In vitro, BQMNPs exhibit multifunctional performance, enabling Cu\n                    <jats:sup>2+<\/jats:sup>\n                    imaging while simultaneously improving cell viability and attenuating inflammatory cytokine expression in Cu\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010induced injury and oxidative stress cell models. In a high\u2010copper\/high\u2010glucose mouse model, the T\u2010MNs module allows sustained BQMNP release for over 10 days, achieving long\u2010acting restoration of copper homeostasis, mitigation of Cu\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010induced hyperglycemia, and systemic detoxification. Remarkably, sustained copper homeostasis regulation markedly suppresses brain inflammation, thereby alleviating Cu\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010mediated tissue injury. Concomitantly, a fast\u2010dissolving D\u2010MNs module provides rapid intradermal Cu\n                    <jats:sup>2+<\/jats:sup>\n                    sensing in vivo, synchronizing Cu\n                    <jats:sup>2+<\/jats:sup>\n                    sensing with prolonged systemic intervention. This temporally programmed theranostic microneedle architecture offers a versatile strategy for precision regulation of metal\u2010ion homeostasis and may inspire new therapeutic approaches for metabolic and neurodegenerative diseases.\n                  <\/jats:p>","DOI":"10.1002\/smll.75829","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T15:26:11Z","timestamp":1790004371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Temporally Programmed Microneedles Platform for Long\u2010Acting Regulation and Rapid Sensing of Systemic Copper Dyshomeostasis"],"prefix":"10.1002","author":[{"given":"Xu\u2010Wei","family":"Qi","sequence":"first","affiliation":[{"name":"Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization Chengdu Institute of Biology Chinese Academy of Sciences  Chengdu China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan University Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u2010Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization Chengdu Institute of Biology Chinese Academy of Sciences  Chengdu China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan University Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu\u2010E","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization Chengdu Institute of Biology Chinese Academy of Sciences  Chengdu China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan University Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Cheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization Chengdu Institute of Biology Chinese Academy of Sciences  Chengdu China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7150-2718","authenticated-orcid":false,"given":"Yi\u2010Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering College of Design and Engineering National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2982-7960","authenticated-orcid":false,"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering College of Design and Engineering National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0405-6883","authenticated-orcid":false,"given":"Bang\u2010Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization Chengdu Institute of Biology Chinese Academy of Sciences  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan University Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4067\/S0716-97602006000100020","article-title":"Understanding Copper Homeostasis in Humans and Copper Effects on Health","volume":"39","author":"Araya M.","year":"2006","journal-title":"Biological Research"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/s41392-022-01229-y","article-title":"Copper Homeostasis and Cuproptosis in Health and Disease","volume":"7","author":"Chen L. 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