Temporal assessment of nanoparticle accumulation after experimental brain injury: Effect of particle size.
Temporal assessment of nanoparticle accumulation after experimental brain injury: Effect of particle size.
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DOI：
10.1038/srep29988
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发表时间：
2016-07-22
影响因子：
4.6
通讯作者：
Stabenfeldt SE
中科院分区：
文献类型：
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作者：
Bharadwaj VN;Lifshitz J;Adelson PD;Kodibagkar VD;Stabenfeldt SE
基于纳米颗粒（NP）的治疗和治疗药物已被开发用于各种疾病，但在神经疾病/损伤方面的应用受到血脑屏障（BBB）的限制。创伤性脑损伤（TBI）导致一系列病理改变，包括血脑屏障的短暂破坏，从而为NP递送到受损脑组织打开了一扇窗。本研究主要研究脑外伤后不同大小NPs的时空累积。具体来说，遭受控制的皮质撞击损伤的动物队列在损伤后立即（0小时）、2小时、5小时、12小时或23小时静脉注射聚乙二醇化NP鸡尾酒（20、40、100和500 nm，每种鸡尾酒都有独特的荧光团）。NPs循环1h后再灌注取脑。共聚焦显微镜显示损伤后1小时内损伤半影内NP积累峰值。发现NP大小与它们在半影区内的持续积累呈反比关系。与顶叶关联区和视觉区相比，NP积累优先发生在损伤半影区的初级运动区和体感觉区。因此，我们表征了损伤后不同时间内高达500 nm的颗粒积聚，表明基于np的TBI治疗在损伤后急性期的潜力。
Nanoparticle (NP) based therapeutic and theranostic agents have been developed for various diseases, yet application to neural disease/injury is restricted by the blood-brain-barrier (BBB). Traumatic brain injury (TBI) results in a host of pathological alterations, including transient breakdown of the BBB, thus opening a window for NP delivery to the injured brain tissue. This study focused on investigating the spatiotemporal accumulation of different sized NPs after TBI. Specifically, animal cohorts sustaining a controlled cortical impact injury received an intravenous injection of PEGylated NP cocktail (20, 40, 100, and 500 nm, each with a unique fluorophore) immediately (0 h), 2 h, 5 h, 12 h, or 23 h after injury. NPs were allowed to circulate for 1 h before perfusion and brain harvest. Confocal microscopy demonstrated peak NP accumulation within the injury penumbra 1 h post-injury. An inverse relationship was found between NP size and their continued accumulation within the penumbra. NP accumulation preferentially occurred in the primary motor and somatosensory areas of the injury penumbra as compared to the parietal association and visual area. Thus, we characterized the accumulation of particles up to 500 nm at different times acutely after injury, indicating the potential of NP-based TBI theranostics in the acute period after injury.