A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes
A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes
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DOI：
10.1038/mt.2010.105
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发表时间：
2010-09-01
影响因子：
12.4
通讯作者：
Zhang, Huang-Ge
中科院分区：
文献类型：
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作者：
Sun, Dongmei;Zhuang, Xiaoying;Zhang, Huang-Ge
单核细胞衍生的骨髓细胞在炎症相关的自身免疫/炎性疾病和癌症中起重要作用。在这里，我们报告说，外来体可以提供抗炎剂，如姜黄素，激活骨髓细胞在体内。这项技术为抗炎药物（如姜黄素）提供了一种靶向炎症细胞的方法，并克服了限制其效用的不必要的脱靶效应。使用外泌体作为递送载体，我们提供证据表明，由外泌体递送的姜黄素在血液中更稳定，浓度更高。我们表明，靶向特异性是由外来体决定的，姜黄素活性的改善是通过将姜黄素导向与治疗相关的炎性细胞而实现的，但不是毒性作用。此外，我们在脂多糖（LPS）诱导的脓毒性休克小鼠模型中验证了该技术的治疗相关性。我们进一步表明，外泌体，而不是单独的脂质，是姜黄素增强抗炎活性所必需的。使用外泌体作为药物载体的特异性为许多炎症相关疾病的治疗创造了机会，而不会因无辜的旁观者或脱靶效应而产生显著的副作用。
Monocyte-derived myeloid cells play vital roles in inflammation-related autoimmune/inflammatory diseases and cancers. Here, we report that exosomes can deliver anti-inflammatory agents, such as curcumin, to activated myeloid cells in vivo. This technology provides a means for anti-inflammatory drugs, such as curcumin, to target the inflammatory cells as well as to overcome unwanted off-target effects that limit their utility. Using exosomes as a delivery vehicle, we provide evidence that curcumin delivered by exosomes is more stable and more highly concentrated in the blood. We show that the target specificity is determined by exosomes, and the improvement of curcumin activity is achieved by directing curcumin to inflammatory cells associated with therapeutic, but not toxic, effects. Furthermore, we validate the therapeutic relevance of this technique in a lipopolysaccharide (LPS)-induced septic shock mouse model. We further show that exosomes, but not lipid alone, are required for the enhanced anti-inflammatory activity of curcumin. The specificity of using exosomes as a drug carrier creates opportunities for treatments of many inflammation-related diseases without significant side effects due to innocent bystander or off-target effects.