Carrier-free functionalized multidrug nanorods for synergistic cancer therapy

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• 作者：Mengjiao Zhou ; Xiujuan Zhang ; Yinlong Yang ; Zhuang Liu ; Baishun Tian ; Jiansheng Jie ; Xiaohong Zhang
• 关键词：Multidrug nanocrystals ; Methotrexate ; 10-Hydroxycamptothecin ; Paclitaxel ; Poly(ethylene glycol)methyl ethers ; Drug delivery
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：November, 2013
• 年：2013
• 卷：34
• 期：35
• 页码：8960-8967
• 全文大小：1895 K

文摘

We developed carrier-free multidrug nanocrystals (MDNCs) for the combination chemotherapy with synergistic effect, improved tolerance and imaging capability for cancer treatment. Three widely used hydrophobic drugs, methotrexate (MTX), 10-hydroxycamptothecin (HCPT) and paclitaxel (PTX), were prepared into one nanorod, and then conjugated with poly(ethylene glycol) (PEG) to improve their water dispersity and bio-environmental stability. It should be noted that only trace amount of PEG was used for surface modification, which ensures a high drug loading capacity of the resulting PEGylated MDNCs. In?vitro studies showed that the MDNCs revealed an obviously higher cytotoxicity than individual drugs in the same dose and suppressed drug resistance against PTX resistant MCF-7/ADR cancer cells, indicating its synergistic effect and improved tolerance. After in?vivo intravenous injection, the MDNCs exhibits a synergetic in?vivo therapeutic effect and possesses obviously superior antitumor effect compared to free multidrugs treatment group and individual drug treatment groups, and no statistically significant weight loss was observed. The MDNCs can also gain imaging capabilities by encapsulated with an organic dye, which render the multidrug nanorod an all-in-one processing system for cancer diagnosis and treatment.