Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer.
Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer.
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用于靶向 shRNA 递送的卵泡刺激素肽缀合纳米颗粒可有效抑制 gro-α 并具有针对卵巢癌的抗肿瘤活性
DOI：
10.1080/10717544.2018.1440667
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发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Xu CJ
中科院分区：
文献类型：
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作者：
Hong SS;Zhang MX;Zhang M;Yu Y;Chen J;Zhang XY;Xu CJ
Abstract The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer.
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影响因子：
4
作者：
Hong S;Zhang X;Chen J;Zhou J;Zheng Y;Xu C
通讯作者：
Xu C
影响因子：
10.8
作者：
Debus, Heiko;Baumhof, Patrick;Kissel, Thomas
通讯作者：
Kissel, Thomas
影响因子：
10.8
作者：
Park, MR;Han, KO;Cho, CS
通讯作者：
Cho, CS
DOI：
10.1038/mtna.2015.23
发表时间：
2015-09-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Lam JK;Chow MY;Zhang Y;Leung SW
通讯作者：
Leung SW
DOI：
10.1158/1078-0432.ccr-13-1536
发表时间：
2013-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Shah V;Taratula O;Garbuzenko OB;Taratula OR;Rodriguez-Rodriguez L;Minko T
通讯作者：
Minko T