Poly(ethylene glycol)-block-poly(ε-caprolactone) micelles for combination drug delivery: evaluation of paclitaxel, cyclopamine and gossypol in intraperitoneal xenograft models of ovarian cancer.
Poly(ethylene glycol)-block-poly(ε-caprolactone) micelles for combination drug delivery: evaluation of paclitaxel, cyclopamine and gossypol in intraperitoneal xenograft models of ovarian cancer.
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聚（乙二醇）-Block-Poly（ε-辅助酮）胶束用于组合药物的胶束：腹膜内腹膜内异种移植物模型的紫杉醇，环皮胺和Gossypol的评估。
DOI：
10.1016/j.jconrel.2012.12.005
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发表时间：
2013-02-28
期刊：
影响因子：
--
通讯作者：
Kwon GS
中科院分区：
文献类型：
--
作者：
Cho H;Lai TC;Kwon GS
卵巢癌是最致命的妇科恶性肿瘤，其特征是化疗耐药率高。目前卵巢癌的治疗策略集中在细胞毒性剂和分子靶向剂的新型药物组合或通常涉及腹膜内（IP）注射的新型药物递送策略。聚（乙二醇）-嵌段-聚（ε-己内酯）（PEG-b-PCL）胶束负载紫杉醇（细胞毒性剂），环巴胺（hedgehog抑制剂），棉酚（Bcl-2抑制剂）。在侧重于组合药物增溶的物理化学研究之后，在体外2-D和3-D细胞培养物中以及在卵巢癌异种移植模型中在体内评价3-药物PEG-b-PCL胶束，跟踪IP注射后ES-2和SKOV 3人卵巢癌细胞系的生物发光信号。3-与紫杉醇相比，药物PEG-b-PCL胶束在2-D细胞培养物中的效力并不显著更强;然而，它们使ES-2肿瘤球状体分解，而单一药物或2-药物组合仅减缓ES-2肿瘤球状体的生长或没有明显的作用。在ES-2和SKOV 3异种移植模型中，基于生物发光成像、3′-脱氧-3 ′-18 F-氟胸苷（18 F-FLT）PET成像和总生存期，3-药物PEG-b-PCL胶束的肿瘤负荷显著低于紫杉醇。18F-FLT-PET图像清楚地显示，与紫杉醇和载体对照相比，3-药物PEG-b-PCL胶束显著减少肿瘤体积。总之，PEG-b-PCL胶束使得能够IP组合递送紫杉醇、环巴胺和棉酚，导致肿瘤生长抑制和比单独紫杉醇更长的存活。这些结果验证了基于细胞毒性剂和分子靶向剂的药物组合的卵巢癌的新治疗策略，所述药物组合通过纳米级药物递送系统（例如PEG-b-PCL胶束）同时递送。
Ovarian cancer is the most lethal gynecological malignancy, characterized by a high rate of chemoresistance. Current treatment strategies for ovarian cancer focus on novel drug combinations of cytotoxic agents and molecular targeted agents or novel drug delivery strategies that often involve intraperitoneal (IP) injection. Poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles were loaded with paclitaxel (cytotoxic agent), cyclopamine (hedgehog inhibitor), and gossypol (Bcl-2 inhibitor). After physicochemical studies focusing on combination drug solubilization, 3-drug PEG-b-PCL micelles were evaluated in vitro in 2-D and 3-D cell culture and in vivo in xenograft models of ovarian cancer, tracking bioluminescence signals from ES-2 and SKOV3 human ovarian cancer cell lines after IP injection. 3-drug PEG-b-PCL micelles were not significantly more potent in 2-D cell culture in comparison to paclitaxel; however, they disaggregated ES-2 tumor spheroids, whereas single drugs or 2-drug combinations only slowed growth of ES-2 tumor spheroids or had no noticeable effects. In ES-2 and SKOV3 xenograft models, 3-drug PEG-b-PCL micelles had significantly less tumor burden than paclitaxel based on bioluminescence imaging, 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) PET imaging, and overall survival. 18F-FLT-PET images clearly showed that 3-drug PEG-b-PCL micelles dramatically reduce tumor volumes over paclitaxel and vehicle controls. In summary, PEG-b-PCL micelles enable the IP combination drug delivery of paclitaxel, cyclopamine and gossypol, resulting in tumor growth inhibition and prolonged survival over paclitaxel alone. These results validate a novel treatment strategy for ovarian cancer based on drug combinations of cytotoxic agents and molecular targeted agents, delivered concurrently by a nanoscale drug delivery system, e.g. PEG-b-PCL micelles.
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影响因子：
3.7
作者：
McCann CK;Growdon WB;Kulkarni-Datar K;Curley MD;Friel AM;Proctor JL;Sheikh H;Deyneko I;Ferguson JA;Vathipadiekal V;Birrer MJ;Borger DR;Mohapatra G;Zukerberg LR;Foster R;Macdougall JR;Rueda BR
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Rueda BR
影响因子：
3
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Reed, John C.
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5.5
作者：
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Fasih, Najla
影响因子：
8.8
作者：
Vassileva, V.;Moriyama, E. H.;De Souza, R.;Grant, J.;Allen, C. J.;Wilson, B. C.;Piquette-Miller, M.
通讯作者：
Piquette-Miller, M.
影响因子：
3.7
作者：
Jensen MM;Erichsen KD;Björkling F;Madsen J;Jensen PB;Højgaard L;Sehested M;Kjær A
通讯作者：
Kjær A