[1]陈志伟,韩世松,安泳橙,等.维生素A修饰的纳米载体靶向肝星状细胞沉默TLR4基因并抑制其激活的体外实验研究[J].介入放射学杂志,2020,29(10):1008-1015.
 CHEN Zhiwei,HAN Shisong,AN Yongcheng,et al.Vitamin A- modified nanocarrier for targeted TLR4 siRNA delivery to hepatic stellate cells for anti-fibrotic treatment: an experimental study in vitro[J].journal interventional radiology,2020,29(10):1008-1015.
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维生素A修饰的纳米载体靶向肝星状细胞沉默TLR4基因并抑制其激活的体外实验研究()

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《介入放射学杂志》[ISSN:1008-794X/CN:31-1796/R]

卷:
29
期数:
2020年10
页码:
1008-1015
栏目:
实验研究
出版日期:
2020-10-25

文章信息/Info

Title:
Vitamin A- modified nanocarrier for targeted TLR4 siRNA delivery to hepatic stellate cells for anti-fibrotic treatment: an experimental study in vitro
作者:
陈志伟 韩世松 安泳橙 周智美 陈 烨 林立腾 朱康顺
Author(s):
CHEN Zhiwei HAN Shisong AN Yongcheng ZHOU Zhimei CHEN Ye LIN Liteng ZHU Kangshun.
Department of Minimally Invasive Intervention, Laboratory of Interventional Radiology, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province 510220, China
关键词:
【关键词】 肝纤维化 纳米载体 肝星状细胞 Toll样受体4小干扰RNA
文献标志码:
A
摘要:
【摘要】 目的 制备由维生素A(VA)修饰的纳米载体聚乙二醇(PEG)-聚乙烯亚胺(PEI),用于靶向肝星状细胞(HSC)(LX-2细胞株)输送Toll样受体(TLR)4小干扰RNA(siRNA)。观察和评估VA-PEG-PEI对LX-2细胞转染效率、TLR4/核因子(NF)- κB信号通路和α- 平滑肌肌动蛋白(SMA)表达的影响。方法 采用细胞计数试剂盒(CCK)- 8检测纳米基因药物细胞毒性。通过流式细胞术和荧光显微镜观察纳米药物转染效率。脂多糖(LPS)刺激LX-2细胞,并用不同多聚体[VA- PEG- PEI/TLR4 siRNA(siTLR4)或PEG-PEI/siTLR4]进行转染。蛋白质印迹法(WB)和免疫荧光法分别检测LX-2细胞TLR4/NF-κB信号通路蛋白水平和α-SMA表达。 结果 高浓度(40 μg/mL)VA-PEG-PEI/siTLR4孵育下LX-2细胞仍具有80%以上存活率,表明纳米药物细胞毒性较低。LPS刺激的LX- 2细胞TLR4/NF-κB信号通路水平升高,这种作用经VA-PEG-PEI/siTLR4处理后显著减弱。同时,VA-PEG-PEI/siTLR4能有效地使LX-2细胞失活,这可通过降低纤维化标志物α-SMA表达证明。结论 VA-PEG-PEI/siTLR4能高效转染siRNA,有效下调LX-2细胞中TLR4/NF-κB信号通路和α-SMA表达。本体外实验研究表明,VA-PEG-PEI/siTLR4具有治疗肝纤维化的巨大潜力。

参考文献/References:

[1] Yin C, Evason KJ, Asahina K, et al. Hepatic stellate cells in liver development, regeneration, and cancer[J]. J Clin Invest,2013, 123:1902- 1910.
[2] Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease[J]. Nat Med, 2012, 18:1028- 1040.
[3] Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis[J]. Lancet, 2014, 383:1749- 1761.
[4] Ellis EL, Mann DA. Clinical evidence for the regression of liver fibrosis[J]. J Hepatol, 2012, 56:1171- 1180.
[5] Solis- Herruzo JA, Solis- Munoz P, Munoz Yague T, et al. Molecular targets in the design of antifibrotic therapy in chronic liver disease[J]. Rev Esp Enferm Dig, 2011, 103:310- 323.
[6] Brun P, Castagliuolo I, Pinzani M, et al. Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells[J]. Am J Physiol Gastrointest Liver Physiol, 2005,289:G571- G578.
[7] 朱 楠,张甜甜,吕维富, 等. 诱导型一氧化氮合酶、血小板衍生生长因子- B和脂多糖在布- 加综合征大鼠模型中的表达及意义[J]. 介入放射学杂志, 2019, 28:262- 267.
[8] 伍振辉,孟 娴,胡佳伟, 等. TLR4- MyD88- NF- kB信号通路与肝炎- 肝纤维化- 肝癌轴相关性研究进展[J]. 国际药学研究杂志, 2017, 44:396- 401.
[9] Yu LX, Schwabe RF. The gut microbiome and liver cancer: mechanisms and clinical translation[J]. Nat Rev Gastroenterol Hepatol, 2017, 14:527- 539.
[10] Bai T, Lian LH, Wu YL, et al. Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells[J]. Int Immunopharmacol, 2013, 15:275- 281.
[11] Su H, Wang Y, Gu Y, et al. Potential applications and human biosafety of nanomaterials used in nanomedicine[J]. J Appl Toxicol,2018, 38:3- 24.
[12] 李 鑫,刘凤永,袁宏军, 等. 纳米刀治疗肝癌[J]. 介入放射学杂志, 2017, 26:939- 943.
[13] Boussif O, Lezoualc’h F, Zanta MA, et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine[J]. Proc Natl Acad Sci USA, 1995, 92:7297- 7301.
[14] Shen M, Gong F, Pang P, et al. An MRI- visible non- viral vector for targeted Bcl- 2 siRNA delivery to neuroblastoma[J]. Int J Nanomedicine, 2012, 7:3319- 3332.
[15] Chen Y, Lian G, Liao C, et al. Characterization of polyethylene glycol- grafted polyethylenimine and superparamagnetic iron oxide nanoparticles(PEG- g- PEI- SPION) as an MRI- visible vector for siRNA delivery in gastric cancer in vitro and in vivo[J]. J Gastroenterol, 2013, 48:809- 821.
[16] Sato Y, Murase K, Kato J, et al. Resolution of liver cirrhosis using vitamin A- coupled liposomes to deliver siRNA against a collagen- specific chaperone[J]. Nat Biotechnol, 2008, 26:431- 442.
[17] Ito S, Nagata K. Biology of Hsp47(Serpin H1), a collagen- specific molecular chaperone[J]. Semin Cell Dev Biol, 2017, 62:142- 151.
[18] Yang X, Iyer AK, Singh A, et al. Cluster of differentiation 44 targeted hyaluronic acid based nanoparticles for MDR1 siRNA delivery to overcome drug resistance in ovarian cancer[J]. Pharm Res, 2015, 32:2097- 2109.
[19] Zhu Q, Zou L, Jagavelu K, et al. Intestinal decontamination inhibits TLR4 dependent fibronectin- mediated cross- talk between stellate cells and endothelial cells in liver fibrosis in mice[J]. J Hepatol, 2012, 56:893- 899.
[20] Liu M, Xu Y, Han X, et al. Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF- κB signaling pathway[J]. Sci Rep, 2015, 5:18038.
[21] Zhang P, An K, Duan X, et al. Recent advances in siRNA delivery for cancer therapy using smart nanocarriers[J]. Drug Discov Today, 2018, 23:900- 911..
[22] Qian C, Wang Y, Chen Y, et al. Suppression of pancreatic tumor growth by targeted arsenic delivery with anti- CD44v6 single chain antibody conjugated nanoparticles[J]. Biomaterials, 2013, 34:6175- 6184.

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备注/Memo

备注/Memo:
(收稿日期:2019- 10- 29)
(本文编辑:边 佶)
更新日期/Last Update: 2020-10-19