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Herein, we engineer a near\u2010infrared\u2010II (NIR\u2010II) phototheranostic nanoplatform, CAG\/FD1080@MM\u2010aTRPV4, for synergistic regulation of microglial function and real\u2010time monitoring of PD pathology. We first encapsulated cycloastragenol (CAG), a bioactive compound derived from\n                    <jats:italic>Astragalus<\/jats:italic>\n                    , into liposomes. These liposomes were then fused with biomimetic microglial membrane\u2010loaded FD1080 photothermal imaging agent, followed by modification with a transient receptor potential vanilloid 4 (TRPV4)\u2010targeting antibody. In vitro studies using\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010syn\u2010treated cultured microglia and in vivo studies in an\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010syn\u2010overexpressing mouse model collectively demonstrate the efficacy of our strategy. It not only enables precise microglial delivery of CAG to reprogram metabolism but also sustains lysosomal function via photothermal activation of the TRPV4\/CaMKK\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \/AMPK\/mTOR pathway, ultimately enhancing phagocytosis. Importantly, the encapsulated FD1080 (for microglial tracking) and an anti\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010syn\u2010conjugated indocyanine green (anti\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010syn\u2010ICG) probe enable dual\u2010modality NIR\u2010II photoacoustic\u2010fluorescence imaging, allowing real\u2010time visualization of both microglial dynamics and\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010syn clearance. This work pioneers a photothermal immunomodulation strategy using a Chinese herb\u2010derived compound, presenting a versatile theranostic platform and novel mechanistic insights for microglia\u2010targeted PD therapy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202523380","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:54:09Z","timestamp":1772970849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NIR\u2010II Imaging\u2010Guided Photothermal Activation of a TRPV4\u2010Targeted Nanoplatform Delivering Cycloastragenol to Promote Microglia Reprogramming and \u03b1\u2010Synuclein Clearance in Parkinson's Disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3929-7633","authenticated-orcid":false,"given":"Hsuan","family":"Lo","sequence":"first","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjuan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Geriatrics Fujian Institute of Geriatrics Fujian Medical University Union Hospital  Fuzhou P. R. China"},{"name":"Fujian Key Laboratory of Molecular Neurology and Institute of Neuroscience Fujian Medical University  Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lik Hang Hugo","family":"Tse","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoheng","family":"Ma","sequence":"additional","affiliation":[{"name":"Medical Research Institute Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences) Southern Medical University  Guangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjuan","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3453-1825","authenticated-orcid":false,"given":"Wing\u2010Tak","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic University  Hong Kong P. R. China"},{"name":"The Hong Kong Polytechnic University Shenzhen Research Institute  Shenzhen Guangdong P. R. 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