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撤回:负载5-氟尿嘧啶的甲氧基聚(乙二醇)-聚(丙交酯)纳米颗粒增强抗肿瘤疗效以有效治疗乳腺癌。

RETRACTED: Enhanced antitumor efficacy of 5-fluorouracil loaded methoxy poly(ethylene glycol)-poly(lactide) nanoparticles for efficient therapy against breast cancer.

作者信息

Yuan Zhu, Qu Xiang, Wang Yu, Zhang Dao-Yun, Luo Jian-Cheng, Jia Ning, Zhang Zhong-Tao

机构信息

Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.

Solomon Brothers Medical Institute, 1521 Concord Pike Suite 301, Wilmington, New Castle, DE 19803, USA.

出版信息

Colloids Surf B Biointerfaces. 2015 Apr 1;128:489-497. doi: 10.1016/j.colsurfb.2015.02.048. Epub 2015 Mar 6.

Abstract

In the present study, a novel nanocarrier was developed for the delivery of anticancer drug to the cancer tissues. For this purpose, 5-FU loaded methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) (5-FU NP) based polymeric nanoparticles was designed to increase the chemotherapeutic efficacy against breast cancers. Nanoprecipitation method was used to prepare the drug-loaded nanoparticles. The nanoparticle was evaluated in terms of DLS, TEM, in vitro release kinetics, and in vivo parameters. The average particle diameter of drug loaded NP was ∼110 nm and exhibited a sustained drug release pattern for up to 120 h. The NP exhibited a pH-response drug release pattern with accelerated release at acidic media. The in vitro cytotoxicity assay showed the enhanced cytotoxicity effect of NP formulations in comparison to free drug. The NP system showed remarkable G2/M phase cell cycle arrest with significant amount of apoptosis cells in late and early phase of flow cytometer analysis. Consistently, NP formulation greatly decreased the tumor burden of mice with no sign of adverse effect. TUNEL assay further confirmed the superior anticancer effect of NP formulations which showed a high number of apoptotic cells. The favorable results obtained from this study highlights the potential application of encapsulated 5-FU NP in the treatment of breast cancers. The remarkable anticancer therapeutic efficacy with negligible toxicity profile of 5-FU NP makes it one of the possible alternative for the successful breast cancer therapy.

摘要

在本研究中,开发了一种新型纳米载体,用于将抗癌药物递送至癌组织。为此,设计了负载5-氟尿嘧啶的甲氧基聚(乙二醇)-聚(丙交酯)(mPEG-PLA)(5-FU纳米颗粒)基聚合物纳米颗粒,以提高对乳腺癌的化疗效果。采用纳米沉淀法制备载药纳米颗粒。通过动态光散射(DLS)、透射电子显微镜(TEM)、体外释放动力学和体内参数对纳米颗粒进行了评估。载药纳米颗粒的平均粒径约为110 nm,并呈现长达120小时的药物持续释放模式。该纳米颗粒呈现pH响应药物释放模式,在酸性介质中释放加速。体外细胞毒性试验表明,与游离药物相比,纳米颗粒制剂的细胞毒性作用增强。纳米颗粒系统在流式细胞仪分析的晚期和早期均显示出显著的G2/M期细胞周期阻滞,并有大量凋亡细胞。一致地,纳米颗粒制剂大大降低了小鼠的肿瘤负担,且无不良反应迹象。TUNEL检测进一步证实了纳米颗粒制剂的优异抗癌效果,显示出大量凋亡细胞。本研究获得的良好结果突出了包封的5-FU纳米颗粒在乳腺癌治疗中的潜在应用。5-FU纳米颗粒具有显著的抗癌治疗效果且毒性可忽略不计,使其成为成功治疗乳腺癌的可能替代方案之一。

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