Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.

Surfactant protein-A nanobody-conjugated liposomes loaded with methylprednisolone increase lung-targeting specificity and therapeutic effect for acute lung injury.
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负载甲基泼尼松龙的表面活性蛋白-A纳米体缀合脂质体可提高急性肺损伤的肺靶向特异性和治疗效果

DOI:
10.1080/10717544.2017.1402217
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发表时间:
2017-11
期刊:
影响因子:
6
通讯作者:
Li HP
Li HP
中科院分区:
医学2区
文献类型:
--
作者:
Li N;Weng D;Wang SM;Zhang Y;Chen SS;Yin ZF;Zhai J;Scoble J;Williams CC;Chen T;Qiu H;Wu Q;Zhao MM;Lu LQ;Mulet X;Li HP

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摘要纳米医学的出现需要新的运载工具来主动靶向其作用部位。在此,我们展示了肺靶向载药脂质体的发展及其有效性、特异性和安全性。我们的研究重点是糖皮质激素甲基强的松龙(MPS),一种常用的药物来治疗肺损伤。将甾体分子装载到官能化的纳米空间稳定的单层脂质体(NSSL)中。通过表面活性剂蛋白A(SPAN b)纳米抗体的缀合以形成MPS-NSSLs-SPAN b来进行靶向功能性。MPS-NSSLs-SPAN b表现出良好的尺寸分布、形态和包封效率。动物实验证明MPS-NSSLs-SPAN b对肺具有高度特异性。MPS-NSSLs-SPAN B b治疗可降低大鼠支气管肺泡灌洗液中TNF-α、IL-8和TGF-β1的水平以及肺组织中NK-κB的表达,从而减轻肺损伤,提高大鼠存活率。当与抗体功能化系统相比时,纳米抗体功能化纳米颗粒显示出治疗肺损伤的上级性能。
Abstract The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS–NSSLs–SPANb. MPS–NSSLs–SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS–NSSLs–SPANb to the lung. Treatment with MPS–NSSLs–SPANb reduced the levels of TNF-α, IL-8, and TGF-β1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.
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