Nasal microenvironment self-responsive herbal hydrogel alleviates Parkinsonian pathology via the inhibition of α-synuclein liquid-liquid phase separation
- Biomaterials. 2026 Jun 1:335:124350. doi: 10.1016/j.biomaterials.2026.124350.
- 1. State Key Laboratory of Traditional Chinese Medicine Syndrome, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
- 2. Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China; Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Engineering Research Center of Xinjiang and Central Asian Medicine Resources, Ministry of Education, College of Pharmacy, Xinjiang Medical University, Urumqi, 830011, China.
- 3. State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi, 830017, China.
- 4. Institute of Integrative Medicine, Department of Integrated Chinese and Western Medicine, Xiangya Hospital Central South University, Changsha, 410008, China.
- 5. Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China.
- 6. The State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, China.
- 7. Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China.
- 8. The State Key Laboratory of Mechanism and Quality of Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, 999078, China. Electronic address: [email protected].
- 9. Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, China. Electronic address: [email protected].
- 10. State Key Laboratory of Traditional Chinese Medicine Syndrome, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. Electronic address: [email protected].
The liquid-liquid phase separation (LLPS) of α-synuclein (α-syn) is recognized as a critical driver of Parkinson's disease (PD) progression. Therefore, inhibiting α-syn LLPS may confer anti-Parkinsonian therapy. Although some small-molecule inhibitors effectively suppress α-syn LLPS, their limited delivery across the blood-brain barrier (BBB) hinders their application. In this study, the natural product baicalein (BA) was found to inhibit α-syn LLPS, and a BA-loaded nasal hydrogel was developed for PD therapy. To avoid the rapid clearance of BA within the nasal cavity, BA was formulated onto the skeleton of carboxymethyl chitosan and 4-formylphenylboronic acid through dynamic intermolecular self-assembly to produce a mucoadhesive hydrogel (CAB2). CAB2 exhibited self-responsive drug release in the weakly acidic and reactive oxygen species-rich microenvironment of the nasal cavity, allowing BA to bypass the BBB and efficiently accumulate in the brain. CAB2 retained the ability of BA to inhibit α-syn LLPS and possessed favorable neuroprotective and anti-neuroinflammatory effects. The therapeutic efficacy of CAB2 extended beyond α-syn LLPS suppression, such that CAB2 also restored autophagic flux, ameliorated oxidative damage, and attenuated neuroinflammatory responses, thus comprehensively remodeling the PD-associated pathological microenvironment. Therefore, this herbal hydrogel capable of self-responsive release in the nasal microenvironment offers a novel therapeutic option for PD.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Mitochondrial MetabolismResearch Areas: Neurological Disease
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