Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells

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• 作者：Rajaletchumy Veloo Kutty ; Chor Yong Tay ; Chen Siew Lim ; Si-Shen Feng…
• 关键词：nanomedicine ; biomaterials ; nanobiology ; biodegradable polymers ; drug targeting
• 刊名：Nano Research
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：8
• 期：8
• 页码：2533-2547
• 全文大小：2,357 KB
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• 作者单位：Rajaletchumy Veloo Kutty (1)
  Chor Yong Tay (1)
  Chen Siew Lim (1)
  Si-Shen Feng (1) (2)
  David Tai Leong (1) (3)
  
  1. Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive, Singapore, 117585, Singapore
  2. International Joint Cancer Institute, The Second Military Medical University, 800 Xiang Yin Road, Shanghai, 200433, China
  3. NUS Graduate School for Integrative Science and Engineering, National University of Singapore, 28 Medical Drive, Singapore, 117456, Singapore
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chinese Library of Science
  Chemistry
  Nanotechnology
  
• 出版者：Tsinghua University Press, co-published with Springer-Verlag GmbH
• ISSN：1998-0000

文摘

A polymer-based nanocarrier was developed for the co-delivery of epigenetic and chemotherapeutic drugs. The sterically stabilized hybrid micelle system uses micelles composed of D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000). In this study, suberoylanilide hydroxamic acid (SAHA) and paclitaxel were used as model drugs for combination chemotherapy to enhance therapeutic efficiency in targeting mesenchyme-like triple negative breast cancer (TNBC) cells. Combination therapy of paclitaxel and SAHA in a dual drug micelle system, (P + S)mic, exhibited an IC50 value of 0.52 μg/mL, which is about 5.91-fold more cytotoxic than the mere combination of free drugs (P + S). Furthermore, the (P + S)mic formulation was far more effective at inhibiting cell migration by more than 3.4-fold than the control. Thus, our findings show that the co-delivery of these drugs using the micelle system greatly enhances their therapeutic effect at a lower dosage, thereby minimizing toxicity. In addition, this formulation is proved to be remarkably effective in preventing cell migration at low dosage.