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This study develops carrier\u2010free nanocapsules (NCs) for targeted delivery of DA and catalase (CAT) to the PD brain, addressing both DA depletion and neuroinflammation simultaneously. The NCs are engineered by DA and 4\u2010formylphenylboronic acid co\u2010loading with cRGD\u2010modified CAT (CAT\u2010cRGD) and surface\u2010modifying with Angiopep\u20102 (Ang). Ang targets the blood\u2010brain barrier (BBB), enhancing brain delivery, while cRGD targets upregulated integrin receptors in the PD\u2010affected BBB. The NCs showed a 1.4\u2010fold increase in parkinsonian brain targeting efficiency compared to normal mice. In PD mice models, NCs demonstrated a stable increase in learning and memory, enhanced locomotor activity, and improved motor coordination. DA supplementation significantly enhanced dopaminergic signaling, increasing DA levels 1.8\u2010 and 3.5\u2010fold in the striatum and substantia nigra, respectively. Additionally, delivered CAT effectively reduced neuroinflammation by mitigating endoplasmic reticulum stress, slowing disease progression, and protecting DA from oxidation. This innovative approach using PD\u2010targeted NCs represents a synergistic strategy for PD treatment, combining symptomatic relief with disease progression intervention.<\/jats:p>","DOI":"10.1002\/advs.202404717","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T05:21:59Z","timestamp":1729488119000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Parkinson Disease \u2010Targeted Nanocapsules for Synergistic Treatment: Combining Dopamine Replacement and Neuroinflammation Mitigation"],"prefix":"10.1002","volume":"11","author":[{"given":"Ziyao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine Xiangya Hospital Central South University  Changsha 410008 China"},{"name":"Key Laboratory of Biological Nanotechnology of National Health Commission Xiangya Hospital, Central South University  Changsha 410008 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