Chemosensitization of cancer cells by siRNA using targeted nanogel delivery.
Chemosensitization of cancer cells by siRNA using targeted nanogel delivery.
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DOI：
10.1186/1471-2407-10-10
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发表时间：
2010-01-11
期刊：
影响因子：
3.8
通讯作者：
McDonald JF
中科院分区：
文献类型：
--
作者：
Dickerson EB;Blackburn WH;Smith MH;Kapa LB;Lyon LA;McDonald JF
化疗耐药是癌症治疗的主要障碍。增强癌细胞对化疗药物敏感性的靶向治疗有可能提高药物疗效，同时减少对非靶向细胞的毒性作用。RNA干扰（RNAi）靶向癌症治疗是一种相对较新的方法，可以通过选择性靶向基因（如表皮生长因子受体（EGFR））来实现体内基因的可逆沉默，EGFR已被证明可以增加癌细胞对紫杉烷化疗的敏感性。然而，递送是RNAi疗法广泛发展的主要障碍。我们在这里报道了使用核/壳水凝胶纳米颗粒（纳米凝胶）功能化的肽，专门针对EphA2受体递送靶向EGFR的小干扰rna （sirna）。免疫印迹法检测EGFR的表达，研究siRNA传递后EGFR表达降低对卵巢癌细胞化疗致敏的影响。负载sirna的肽靶向纳米凝胶处理EphA2阳性Hey细胞可降低EGFR表达水平，显著提高该细胞系对多西紫杉醇的敏感性（P < 0.05）。EphA2表达阴性的SK-OV-3细胞经纳米凝胶处理后，EGFR水平未降低，多西他赛敏感性未增加（P < 0.05）。这项研究表明，通过纳米凝胶靶向递送sirna可能是一种很有前途的策略，可以提高化疗药物治疗卵巢癌的疗效。此外，EphA2是一个可行的治疗递送靶点，并且sirna受到纳米凝胶载体的有效保护，克服了阻碍治疗性sirna临床进展的稳定性和摄取性差的问题。
Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics. We report here the use of core/shell hydrogel nanoparticles (nanogels) functionalized with peptides that specially target the EphA2 receptor to deliver small interfering RNAs (siRNAs) targeting EGFR. Expression of EGFR was determined by immunoblotting, and the effect of decreased EGFR expression on chemosensitization of ovarian cancer cells after siRNA delivery was investigated. Treatment of EphA2 positive Hey cells with siRNA-loaded, peptide-targeted nanogels decreased EGFR expression levels and significantly increased the sensitivity of this cell line to docetaxel (P < 0.05). Nanogel treatment of SK-OV-3 cells, which are negative for EphA2 expression, failed to reduce EGFR levels and did not increase docetaxel sensitivity (P > 0.05). This study suggests that targeted delivery of siRNAs by nanogels may be a promising strategy to increase the efficacy of chemotherapy drugs for the treatment of ovarian cancer. In addition, EphA2 is a viable target for therapeutic delivery, and the siRNAs are effectively protected by the nanogel carrier, overcoming the poor stability and uptake that has hindered clinical advancement of therapeutic siRNAs.
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影响因子：
3.9
作者：
Kang, CS;Pu, PY;Wang, GX
通讯作者：
Wang, GX
影响因子：
5.2
作者：
Larsen, Alice Bjerregaard;Pedersen, Mikkel Wandahl;Poulsen, Hans Skovgaard
通讯作者：
Poulsen, Hans Skovgaard
影响因子：
8
作者：
Brantley, DM;Cheng, N;Chen, J
通讯作者：
Chen, J
影响因子：
15.9
作者：
Brantley-Sieders, Dana M.;Zhuang, Guanglei;Chen, Jin
通讯作者：
Chen, Jin
DOI：
10.1073/pnas.90.20.9552
发表时间：
1993-10-15
影响因子：
11.1
作者：
JORDAN, MA;TOSO, RJ;WILSON, L
通讯作者：
WILSON, L