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Herein, we developed the ROS (reactive oxygen species)\u2010responsive brain neuronal targeting nanotheranostic platforms that possess the dual\u2010channel fluorescent \u201cturn\u2010on\u201d properties and release drugs in AD neurons in response to ROS, thereby simultaneously facilitating the diagnosis and therapy of early AD. Through the modification of acetylcholine receptor targeting RVG29 peptide, the nanotheranostics penetrated BBB and accumulated into diseased neurons in an intact form, consequently maximizing the diagnostic and therapeutic performance. The anti\u2010oxidative drug baicalein conjugated onto the surface of nanotheranostics via ROS\u2010cleavable boronate ester linkage rapidly released for ROS scavenging, while the encapsulated fluorophores turned on their fluorescence for AD diagnosis upon microenvironment stimuli. This nanotheranostic strategy exhibited highly sensitivity with a ROS detection limit of up to 100\u00a0\u00b5\n                    <jats:sc>m<\/jats:sc>\n                    and accurately early detection of ROS in 3\u00d7Tg AD mice at 6 months of age in vivo. In addition, it could also rescue memory defects, scavenge oxidative stress, attenuate neuroinflammation and enhance neuroprotective effect in 3\u00d7Tg AD mice. This work opens up a promising and smart strategy for early diagnosis and therapy in neurodegenerative disease.\n                  <\/jats:p>","DOI":"10.1002\/smll.202403980","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T02:55:58Z","timestamp":1729479358000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Redox Oxygen Species\u2010Responsive Nanotheranostics with Dual\u2010Channel Fluorescent Turn\u2010On for Early Diagnosis and Targeted Therapy of Alzheimer's Disease"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-2628","authenticated-orcid":false,"given":"Qian","family":"Guo","sequence":"first","affiliation":[{"name":"Shanghai 411 Hospital China RongTong Medical Healthcare Group Co.Ltd. \/ 411 Hospital Shanghai University  Shanghai 200081 China"},{"name":"Laboratory of Drug Delivery School of Medicine Shanghai University  99 Shangda Road Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianying","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Fudan University  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Qian","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong  NT Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Drug Delivery School of Medicine Shanghai University  99 Shangda Road Shanghai 200444 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,20]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"A. 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