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However, nose\u2010to\u2010brain delivery confronts sequential obstacles, including mucosal penetration, lesion\u2010specific accumulation, and active targeting toward disease\u2010relevant cells, demanding advanced nanotherapeutic design. Meanwhile, neural mitochondrial dysfunction and neuroinflammation constitutes two cross\u2010interfering pathogeneses that drive PD progression. Herein, we developed an intelligent biomimetic nanoplatform (hPH\u2011RNPEC) based on\n                    <jats:italic>Pueraria lobata<\/jats:italic>\n                    \u2010derived exosomes. The system is engineered with neutrophil\u2010like membrane for inflammatory tropism, spatially staggered short unit of rabies virus glycoprotein (RVG) peptide for neuron\u2010microglia dual targeting, and long motif of the tetrablock conjugation of 1,2\u2010distearoyl\u2010sn\u2010glycero\u20103\u2010phosphoethanolamine (DSPE), pH\u2010sensitive hydrazone bond, polyethylene glycol 2000 (PEG2k), and a histidine\u2010switching peptide for efficient nasal mucosal penetration. Spatiotemporally, following intranasal administration in PD mice, hPH\u2011RNPEC can penetrate nasal mucosa, achieve inflammation\u2011directed lesion accumulation, and realize efficient cellular internalization. The system also co\u2011delivers endogenous exosomal miRNAs and therapeutic curcumin to mitigate neural mitochondrial damage and neuroinflammation collectively evidenced by mitochondrial function and inflammation assessment. Besides, single\u2010cell RNA sequencing (scRNA\u2010seq) further suggested the promotion of myelin repair and rewiring of neural circuits, which facilitate the remodeling of PD microenvironment. This study establishes an engineered biomimetic nanorobot platform for precise brain targeting and multifactorial intervention for PD treatment.\n                  <\/jats:p>","DOI":"10.1002\/smll.202513394","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:04:53Z","timestamp":1769673893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Engineered Biomimetic Nanorobots Orchestrate Targeted Nose\u2010to\u2010Brain Delivery to Resolve Neuron\u2010Glia Entanglement against Parkinson's Disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Yang","family":"Xu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang University  Hangzhou P. R. 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