Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression.
Arrowtail RNA for Ligand Display on Ginger Exosome-like Nanovesicles to Systemic Deliver siRNA for Cancer Suppression.
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DOI：
10.1038/s41598-018-32953-7
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发表时间：
2018-10-02
影响因子：
4.6
通讯作者：
Guo P
中科院分区：
文献类型：
--
作者：
Li Z;Wang H;Yin H;Bennett C;Zhang HG;Guo P
外切体作为治疗囊泡的潜力越来越大，但在成本/产量、药物有效载荷和靶向性等方面仍然存在挑战。植物来源的类外切体纳米粒已被报道为一种很有前途的替代品，并通过口服、鼻腔给药显示出生物相容性；然而，直接从植物中分离出来的类外显子纳米粒系统性地传递siRNA的报道尚未见报道。最近，我们报道了用细胞靶向配体来控制RNA的取向来修饰人来源的外体，从而将siRNA特异性地运送到肿瘤中。在这里，我们扩展到应用箭尾RNA纳米颗粒在生姜衍生的外周体样纳米颗粒(GDEN)上展示配体，用于siRNA递送和通过静脉注射抑制肿瘤。采用缓冲超速离心法和平衡密度梯度超速离心法分离纯化GDEN，其大小、密度和形态与人来源的外切体相似。叶酸(FA)作为配体被展示在GDEN的表面，用于靶向地将Survivin siRNA传递到KB肿瘤模型。在体外，FA-3WJ/GDENS/siRNA复合体的基因敲除效率与转染法相当。我们通过静脉给药在异种移植模型上观察到了肿瘤生长的抑制，这揭示了GDEN作为一种经济的siRNA递送系统的潜力。
Exosomes have shown increasing potential as delivery vesicles for therapy, but challenges like cost/yield, drug payload, and targeting specificity still exist. Plant derived exosome-like nanoparticles have been reported as a promising substitution and exhibit biocompatibility through oral, intranasal administration; however, systemic delivery of siRNA by exosome-like nanoparticles directly isolated from plants has not been reported. Recently, we reported the control of RNA orientation to decorate human derived exosome with cell targeting ligands for specific delivery of siRNA to tumors. Here, we expand to the application of arrowtail RNA nanoparticles for displaying ligands on ginger derived exosome-like nanovesicles (GDENs) for siRNA delivery and tumor inhibition through IV administration. Cushion ultracentrifugation coupled with equilibrium density gradient ultracentrifugation were used for purifying GDENs that displayed size, density, and morphology similar to human derived exosomes. Folic acid (FA), as a ligand, was displayed on the surface of GDENs for targeted delivery of survivin siRNA to KB cancer models. In vitro gene knockdown efficacy by FA-3WJ/GDENs/siRNA complex was comparable to transfection. We observed inhibition of tumor growth on a xenograft model by intravenous administration, which reveals the potential of GDENs as an economic delivery system for siRNA.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
17.1
作者：
Shu D;Zhang H;Petrenko R;Meller J;Guo P
通讯作者：
Guo P
影响因子：
9.7
作者：
Munagala R;Aqil F;Jeyabalan J;Gupta RC
通讯作者：
Gupta RC
影响因子：
56.9
作者：
GUO, PX;ERICKSON, S;ANDERSON, D
通讯作者：
ANDERSON, D
影响因子：
10.8
作者：
Shu, D;Moll, WD;Guo, PX
通讯作者：
Guo, PX