Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Republic of Korea.
Department of Bioscience and Biotechnology, Konkuk University, Seoul, 143-701, Republic of Korea.
Biomaterials. 2018 Apr;162:71-81. doi: 10.1016/j.biomaterials.2018.02.003. Epub 2018 Feb 3.
To determine whether exosomes are efficient carriers for immune stimulating molecules into lymph nodes, comparative studies of exosomes (EXOs) derived from different origins (cells and serums) in terms of physicochemical properties and delivery efficiency were performed. Serum-derived EXOs were of a preferable size and generated higher yields than RAW264.7 cell-derived exosomes (RAW-EXO). In particular, fetal bovine serum-derived exosomes (bo-EXO), with a size below 50 nm, were delivered not only to surface zones (subcapsular sinus (SCS) macrophage zone) but also to inner paracortex zones (T cell zone) of lymph nodes, which allowed an efficient delivery of immune stimulating molecules to antigen presenting cells and T cells. The encapsulation of immune stimulating biomolecules (monophosphoryl lipid A (MPLA) and CpG oligodeoxynucleotides (CpG ODN)) within EXOs greatly increased intracellular delivery to macrophages via phagocytic pathways, which induced higher TNF-α and IL-6 secretion than free MPLA and free CpG ODN. MPLA-incorporated exosomes activated and differentiated T cells after subcutaneous injection, which elevated cytokine IFN-γ and TNF-α induction for CD3 T cells. Taken together, bo-EXOs might serve as efficient carrier systems of immune stimulators to lymph nodes for desired immune responses.
为了确定外泌体是否是将免疫刺激分子有效递送至淋巴结的载体，我们对源自不同来源（细胞和血清）的外泌体（EXO）进行了比较研究，比较了它们在理化性质和递药效率方面的差异。与 RAW264.7 细胞来源的外泌体（RAW-EXO）相比，血清来源的外泌体（EXO）具有更小的粒径和更高的产量。特别是牛血清来源的外泌体（bo-EXO），其粒径小于 50nm，不仅递送至淋巴结表面区（被膜下窦（SCS）巨噬细胞区），而且递送至淋巴结内区（T 细胞区），从而可以将免疫刺激分子有效地递送至抗原呈递细胞和 T 细胞。将免疫刺激生物分子（单磷酰脂质 A（MPLA）和 CpG 寡脱氧核苷酸（CpG ODN））包封在 EXO 内，通过吞噬途径极大地增加了向巨噬细胞的细胞内递药，这导致 TNF-α 和 IL-6 的分泌量高于游离 MPLA 和游离 CpG ODN。MPLA 包封的外泌体在皮下注射后激活和分化 T 细胞，从而提高了 CD3 T 细胞中细胞因子 IFN-γ 和 TNF-α 的诱导。综上所述，bo-EXO 可能是将免疫刺激剂有效递送至淋巴结以实现所需免疫反应的载体系统。
