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Войти в исследования Journal of controlled release : official journal of the Controlled Release Society · 2025
The use of Xenon magnetic lipid bubbles to detect and treat intermittent hypoxia-induced cognitive impairment.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sun Yang, Miao Yuyang, Dai Shiyin, Wang Kailin, Tan Jin, Jiao Zhen, Zhang Qiang
Аннотация
BACKGROUND: Obstructive sleep apnea (OSA) is closely associated with cognitive impairments caused by intermittent hypoxia (IH)-induced neuronal death. Despite extensive clinical support of its underlying mechanism, effective strategies for targeted delivery of treatments to IH-induced neuronal injury remain limited.
AIMS: This study was designed to develop and evaluate a class of novel and multifunctional nanocarriers that can be used for the diagnosis and treatment of IH-induced cerebral injury.
METHODS: We used the magneto internal heat bubble generation technique to construct magnetic lipid bubbles, which are nanobubbles consisting of a xenon gas core, a phospholipid shell, and embedded superparamagnetic iron oxide nanoparticles (SPIONs) called Xenon Magnetic Lipid Bubbles. We also conjugated LM11A-31, the ligand for the p75 neurotrophin receptor, to the phospholipid shells of Xenon Magnetic Lipid Bubbles to improve their neuronal targeting (LM11A-31-modified Xenon Magnetic Lipid Bubbles). The biosafety, blood-brain barrier permeability, and efficacy of LM11A-31-modified Xenon Magnetic Lipid Bubbles for neuroprotection were evaluated in vitro and in vivo using real-time fluorescence imaging, immunofluorescence staining, cognitive behavioral tests, and neuronal viability assays.
RESULTS: In a mouse model of IH, LM11A-31-modified Xenon Magnetic Lipid Bubbles were accumulated more in the region of injured NeuN+ neurons, and were more efficacious in improving the cognitive performance of IH mice than were Xenon Magnetic Lipid Bubbles. In addition to their therapeutic activity, SPION-containing magnetic lipid bubbles enhanced T2-weighted signals of Magnetic Resonance Imaging (MRI) in a concentration-dependent manner. In the mouse model, magnetic lipid bubbles detected IH-induced early brain injury, as indicated by the reduction of hippocampal volume and the increase in T2-relaxation time of the MRI.
CONCLUSIONS: Xenon Magnetic Lipid Bubbles provide a safe and effective theranostic approach to IH-related neuronal injury. The efficacy is improved by conjugating LM11A-31 to Xenon Magnetic Lipid Bubbles to ensure targeted neuroprotection. SPIONs facilitate enhanced MRI contrast to detect IH-induced cerebral injuries. These findings support the potential of LM11A-31-modified Xenon Magnetic Lipid Bubbles for the diagnosis and treatment of OSA-induced cognitive dysfunction.
AIMS: This study was designed to develop and evaluate a class of novel and multifunctional nanocarriers that can be used for the diagnosis and treatment of IH-induced cerebral injury.
METHODS: We used the magneto internal heat bubble generation technique to construct magnetic lipid bubbles, which are nanobubbles consisting of a xenon gas core, a phospholipid shell, and embedded superparamagnetic iron oxide nanoparticles (SPIONs) called Xenon Magnetic Lipid Bubbles. We also conjugated LM11A-31, the ligand for the p75 neurotrophin receptor, to the phospholipid shells of Xenon Magnetic Lipid Bubbles to improve their neuronal targeting (LM11A-31-modified Xenon Magnetic Lipid Bubbles). The biosafety, blood-brain barrier permeability, and efficacy of LM11A-31-modified Xenon Magnetic Lipid Bubbles for neuroprotection were evaluated in vitro and in vivo using real-time fluorescence imaging, immunofluorescence staining, cognitive behavioral tests, and neuronal viability assays.
RESULTS: In a mouse model of IH, LM11A-31-modified Xenon Magnetic Lipid Bubbles were accumulated more in the region of injured NeuN+ neurons, and were more efficacious in improving the cognitive performance of IH mice than were Xenon Magnetic Lipid Bubbles. In addition to their therapeutic activity, SPION-containing magnetic lipid bubbles enhanced T2-weighted signals of Magnetic Resonance Imaging (MRI) in a concentration-dependent manner. In the mouse model, magnetic lipid bubbles detected IH-induced early brain injury, as indicated by the reduction of hippocampal volume and the increase in T2-relaxation time of the MRI.
CONCLUSIONS: Xenon Magnetic Lipid Bubbles provide a safe and effective theranostic approach to IH-related neuronal injury. The efficacy is improved by conjugating LM11A-31 to Xenon Magnetic Lipid Bubbles to ensure targeted neuroprotection. SPIONs facilitate enhanced MRI contrast to detect IH-induced cerebral injuries. These findings support the potential of LM11A-31-modified Xenon Magnetic Lipid Bubbles for the diagnosis and treatment of OSA-induced cognitive dysfunction.