Cell membrane-formed nanovesicles for disease-targeted delivery.
Cell membrane-formed nanovesicles for disease-targeted delivery.
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DOI：
10.1016/j.jconrel.2016.01.024
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发表时间：
2016-02-28
期刊：
影响因子：
--
通讯作者：
Wang Z
中科院分区：
文献类型：
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作者：
Gao J;Chu D;Wang Z
血管炎症是大多数疾病的潜在组成部分。为了靶向发炎的脉管系统，通常通过将抗体缀合到纳米颗粒表面来设计纳米颗粒，但这种自下而上的方法可能会影响复杂的生理相关系统中纳米颗粒的靶向和治疗效果。在血管炎症期间，内皮通过 NF-κB 通路立即上调细胞间粘附分子 1 (ICAM-1)，该分子与中性粒细胞膜上的整合素 β2 结合。受这种相互作用的启发，我们创建了一种基于纳米囊泡的药物递送系统，利用氮空化作用快速破坏活化的中性粒细胞以制造细胞膜纳米囊泡。使用活体小鼠提睾小静脉的活体显微镜研究表明，这些囊泡可以选择性地结合发炎的脉管系统，因为它们具有完整的整合素 β2 靶向分子。施用载有 TPCA-1（一种 NF-κB 抑制剂）的纳米囊泡可显着减轻小鼠急性肺部炎症。我们的研究揭示了一种新的自上而下的策略，可直接利用患病组织来生产基于生物功能的纳米囊泡药物输送系统，该系统可用于治疗各种疾病。
Vascular inflammation is underlying components of most diseases. To target inflamed vasculature, nanoparticles are commonly engineered by conjugating antibody to the nanoparticle surface, but this bottom-up approach could affect nanoparticle targeting and therapeutic efficacy in complex, physiologically related systems. During vascular inflammation endothelium via the NF-κB pathway instantly upregulates intercellular adhesion molecule 1 (ICAM-1) which binds integrin β2 on neutrophil membrane. Inspired by this interaction, we created a nanovesicle-based drug delivery system using nitrogen cavitation which rapidly disrupts activated neutrophils to make cell membrane nanovesicles. Studies using intravital microscopy of live mouse cremaster venules showed that these vesicles can selectively bind inflamed vasculature because they possess intact targeting molecules of integrin β2. Administering of nanovesicles loaded with TPCA-1 (a NF-κB inhibitor) markedly mitigated mouse acute lung inflammation. Our studies reveal a new top-down strategy for directly employing a diseased tissue to produce biofunctional nanovesicle-based drug delivery systems potentially applied to treat various diseases.