Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro.
Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro.
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DOI：
10.1186/1757-2215-6-80
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发表时间：
2013-11-20
影响因子：
4
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Hong S;Zhang X;Chen J;Zhou J;Zheng Y;Xu C
RNA干扰技术在癌症治疗中显示出很高的治疗潜力。然而，血清不稳定、组织通透性差以及对短干扰RNA(SiRNA)的非特异性摄取限制了其在体内的应用。为了克服这些限制并提高卵巢癌的特异性，我们开发了一种针对siRNA的靶向纳米颗粒递送系统。该系统包括卵泡刺激素β33-53肽作为靶向部分，特异性识别卵巢癌细胞上表达的卵泡刺激素受体。生长调节癌基因α(GRO-α)已被报道参与卵巢癌的发生发展。因此，针对GRO-α的小干扰RNA被用作该递送系统中的抗肿瘤药物。制备了β33-53多肽偶联小干扰RNA聚乙二醇-聚乙烯亚胺纳米粒(FSH33-G-NP)，并用凝胶阻滞法和透射电子显微镜对其进行了表征。测定了颗粒大小和Zeta电位。用实时荧光定量RT-α、免疫细胞化学和酶联免疫吸附试验检测GRO-GRNAmRNA和蛋白的表达。用细胞计数试剂盒8法、细胞划痕实验和Transwell迁移实验检测卵巢透明细胞癌细胞系ES-2的增殖、迁移和侵袭能力。获得了有效沉默gro-α表达的siRNA序列，并将其装载到靶向递送系统中。与未修饰α的Gro-FSHsiRNA纳米粒(G-NP)相比，FSH33-G-NP在基因和蛋白水平均显著下调ES-2细胞中Gro-α的表达。因此，沉默gro-α表达后，ES-2细胞的增殖、迁移和侵袭等侵袭性生物学行为受到抑制，而β33-53肽的加入增强了这种抑制作用。本研究表明，FSHR介导的递送系统可以介导siRNA高选择性地导入卵巢癌细胞，沉默gro-α的表达可能成为卵巢癌治疗的一种潜在选择。
RNA interference technology has shown high therapeutic potential for cancer treatment. However, serum instability, poor tissue permeability and non-specific uptake of short interfering RNA (siRNA) limit its administration in vivo. To overcome these limitations and improve the specificity for ovarian cancer, we developed a targeted nanoparticle delivery system for siRNA. This system included follicle-stimulating hormone (FSH) β 33–53 peptide as a targeting moiety that specifically recognized FSH receptor (FSHR) expressed on ovarian cancer cells. Growth regulated oncogene α (gro-α) has been reported to be involved in ovarian cancer development and progression. Thus, siRNA targeted to gro-α was used as an antitumor drug in this delivery system. FSH β 33–53 peptide-conjugated gro-α siRNA-loaded polyethylene glycol (PEG)-polyethylenimine (PEI) nanoparticles (FSH33-G-NP) were prepared and characterized by gel retardation assay and transmission electron microscopy. Particle size and zeta potential were determined. Expression of gro-α mRNA and protein was detected by real-time quantitative RT-PCR, immunocytochemistry and enzyme-linked immunosorbent assay. The proliferation, migration and invasion of the ovarian clear cell carcinoma cell line ES-2 were evaluated by cell counting kit-8 assay, cell scratch assay and transwell migration assay. A siRNA sequence that is effective in silencing gro-α expression was obtained and loaded into the targeted delivery system. Compared with gro-α siRNA-loaded nanoparticles without FSH peptide modification (G-NP), FSH33-G-NP significantly down-regulated gro-α expression in ES-2 cells at mRNA and protein levels. Consequently, the aggressive biological behaviors of ES-2 cells, including proliferation, migration and invasion, were suppressed after silencing gro-α expression, and the addition of the FSH β 33–53 peptide enhanced the suppressive effects. This study indicated that a FSHR-mediated delivery system could mediate the highly selective delivery of siRNA into ovarian cancer cells and that silencing gro-α expression could be a potential choice for ovarian cancer treatment.
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影响因子：
3.8
作者：
Rubie C;Frick VO;Wagner M;Schuld J;Gräber S;Brittner B;Bohle RM;Schilling MK
通讯作者：
Schilling MK
DOI：
10.1046/j.1365-2036.2000.014s1094.x
发表时间：
2000-04-01
影响因子：
7.6
作者：
Suzuki, H;Mori, M;Ishii, H
通讯作者：
Ishii, H
影响因子：
3.8
作者：
Bandapalli, Obul R.;Ehrmann, Franziska;Brand, Karsten
通讯作者：
Brand, Karsten
影响因子：
64.5
作者：
Kuilman, Thomas;Michaloglou, Chrysiis;Peeper, Daniel S.
通讯作者：
Peeper, Daniel S.
影响因子：
6.6
作者：
Chen Y;Huang L
通讯作者：
Huang L