血脑屏障
肽
细胞内
药物输送
生物物理学
化学
表面改性
纳米颗粒
药理学
细胞生物学
纳米技术
生物化学
中枢神经系统
材料科学
生物
神经科学
有机化学
物理化学
作者
Daniela Guarnieri,Annarita Falanga,Ornella Muscetti,Rossella Tarallo,Sabato Fusco,Massimiliano Galdiero,Stefania Galdiero,Paolo A. Netti
出处
期刊:Small
[Wiley]
日期:2012-11-07
卷期号:9 (6): 853-862
被引量:87
标识
DOI:10.1002/smll.201201870
摘要
Abstract Many therapeutic drugs are excluded from entering the brain due to their lack of transport through the blood–brain barrier (BBB). The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. To overcome this problem, a viral fusion peptide (gH625) derived from the glycoprotein gH of Herpes simplex virus type 1 is developed, which possesses several advantages including high cell translocation potency, absence of toxicity of the peptide itself, and the feasibility as an efficient carrier for delivering therapeutics. Therefore, it is hypothesized that brain delivery of nanoparticles conjugated with gH625 should be efficiently enhanced. The surface of fluorescent aminated polystyrene nanoparticles (NPs) is functionalized with gH625 via a covalent binding procedure, and the NP uptake mechanism and permeation across in vitro BBB models are studied. At early incubation times, the uptake of NPs with gH625 by brain endothelial cells is greater than that of the NPs without the peptide, and their intracellular motion is mainly characterized by a random walk behavior. Most importantly, gH625 peptide decreases NP intracellular accumulation as large aggregates and enhances the NP BBB crossing. In summary, these results establish that surface functionalization with gH625 may change NP fate by providing a good strategy for the design of promising carriers to deliver drugs across the BBB for the treatment of brain diseases.
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