A Novel Nanoparticle Drug Delivery System: The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes

被引:1433
作者
Sun, Dongmei [2 ]
Zhuang, Xiaoying [1 ,3 ]
Xiang, Xiaoyu [1 ,3 ]
Liu, Yuelong [3 ]
Zhang, Shuangyin [3 ]
Liu, Cunren [3 ]
Barnes, Stephen [4 ]
Grizzle, William [5 ]
Miller, Donald [1 ]
Zhang, Huang-Ge [1 ,3 ,6 ,7 ]
机构
[1] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40202 USA
[2] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA
[3] Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA
[4] Univ Alabama, Dept Pharmacol, Birmingham, AL 35294 USA
[5] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA
[6] Birmingham Vet Adm Med Ctr, Birmingham, AL USA
[7] Univ Louisville, Brown Canc Ctr, Dept Microbiol & Immunol, Louisville, KY 40202 USA
基金
美国国家卫生研究院;
关键词
SUPPRESSOR-CELLS; DENDRITIC CELLS; MYELOID CELLS; IN-VITRO; TUMOR PROGRESSION; BLOOD MONOCYTES; INFLAMMATION; CANCER; AUTOIMMUNE; LIPOSOME;
D O I
10.1038/mt.2010.105
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
收藏
页码:1606 / 1614
页数:9
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