Intranasal liposomes co-delivery of Aβ-targeted KLVFF and ROS-responsive ceria for synergistic therapy of Alzheimer’s disease

Schematic illustrations of KLVFF@LIP-CeO2 for the treatment of AD. (a) Preparation of KLVFF@LIP-CeO2 by a thin-film hydration and extrusion method. (b) KLVFF@LIP-CeO2 is intranasally delivered to APP/PS1 mice. KLVFF can inhibit Aβ aggregation via hydrogen-bonding interactions, whilst CeO2 can scaven...

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Veröffentlicht in:Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2024-08, Vol.494, p.153210, Article 153210
Hauptverfasser: Shan, Qiujie, Zhi, Yue, Chen, Yi, Yao, Weina, Zhou, Huijuan, Che, Junyi, Bai, Feng
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Sprache:eng
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Zusammenfassung:Schematic illustrations of KLVFF@LIP-CeO2 for the treatment of AD. (a) Preparation of KLVFF@LIP-CeO2 by a thin-film hydration and extrusion method. (b) KLVFF@LIP-CeO2 is intranasally delivered to APP/PS1 mice. KLVFF can inhibit Aβ aggregation via hydrogen-bonding interactions, whilst CeO2 can scavenge multi-ROS via facile redox switching between Ce4+ and Ce3+. This system can simultaneously alleviate Aβ deposition and oxidative stress in APP/PS1 mice, corporately resulting in the neuroprotective effects and the rescue of cognitive impairment. [Display omitted] •KLVFF@LIP-CeO2 enabled co-delivery of Aβ-degrading peptide and ROS-scavenging nanozyme for synergistic therapy of AD.•Intranasal administration enabled sufficient drug accumulation inbrain.•KLVFF@LIP-CeO2 alleviated Aβ deposition and oxidative stress, contributing torscue of cognitive impairment of APP/PS1 mice. β-Amyloid (Aβ) aggregation and oxidative stress are primary pathological features of Alzheimer’s disease (AD). Combination therapies that target brain tissue and corporately address these main pathological factors are required for effective AD treatment. Here, we developed a multifunctional liposome delivery system (KLVFF@LIP-CeO2) for co-delivery of Aβ-targeted KLVFF and reactive oxygen species (ROS)-responsive Ceria (CeO2) through intranasal administration. After Aβ1-42-induced ROS and apoptosis in HT22 cells, KLVFF@LIP-CeO2 exhibited significant protective effects by inhibiting Aβ aggregation and scavenging multi-ROS. With these features, we verified the therapeutic effectiveness of KLVFF@LIP-CeO2 in APPswe/PSEN1dE9 (APP/PS1) model mice. After intranasal administration, KLVFF@LIP-CeO2 demonstrated sufficient and rapid accumulation in the brain and significantly alleviated Aβ deposition and oxidative stress, corporately contributing to the rescue of cognitive impairment of APP/PS1 mice. These results highlight the clinical potential of these multi-targeted nanoparticles for synergistic therapy of AD.
ISSN:1385-8947
DOI:10.1016/j.cej.2024.153210