Counteracting Alzheimer's disease <i>via</i> normalizing neurovascular unit with a self-regulated multi-functional nano-modulator.

Xue XIA; Ya WEI; Qianqian HUANG; Yang ZHOU; Xiaorong WANG; Yulong SHI; Xiaotong YANG; Wenqin YANG; Yiwei ZHANG; Ting LEI; Yuan HUANG; Hanmei LI; Meng QIN; Huile GAO

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Counteracting Alzheimer's disease via normalizing neurovascular unit with a self-regulated multi-functional nano-modulator.

Author: Xue XIA ¹ ; Ya WEI ¹ ; Qianqian HUANG ¹ ; Yang ZHOU ¹ ; Xiaorong WANG ¹ ; Yulong SHI ¹ ; Xiaotong YANG ¹ ; Wenqin YANG ¹ ; Yiwei ZHANG ¹ ; Ting LEI ¹ ; Yuan HUANG ¹ ; Hanmei LI ² ; Meng QIN ¹ ; Huile GAO ¹
Author Information

1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu 610041, China.
2. Key Laboratory of Coarse Cereal Processing, School of Food and Biological Engineering, Chengdu University, Chengdu 610106, China.
Publication Type:Journal Article
Keywords: Alzheimer's disease; Anti-inflammation; Gene delivery; Neurovascular unit; Pathological blood–brain barrier; Receptor for advanced glycation end products; Synergetic therapy; Targeted delivery
From: Acta Pharmaceutica Sinica B 2024;14(12):5464-5478
CountryChina
Language:English
Abstract: The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.