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首页> 外文期刊>Molecular pharmaceutics >Methotrexate-loaded PEGylated chitosan nanoparticles: Synthesis, characterization, and in vitro and in vivo antitumoral activity
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Methotrexate-loaded PEGylated chitosan nanoparticles: Synthesis, characterization, and in vitro and in vivo antitumoral activity

机译：甲氨蝶呤负载的聚乙二醇化壳聚糖纳米粒子：合成，表征，以及体外和体内的抗肿瘤活性

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Cancer nanotherapeutics are rapidly progressing and being implemented to solve several limitations of conventional drug delivery systems. In this paper, we report a novel strategy of preparing methotrexate (MTX) nanoparticles based on chitosan (CS) and methoxypoly(ethylene glycol) (mPEG) used as nanocarriers to enhance their targeting and prolong blood circulation. MTX and mPEG-conjugated CS nanoparticles (NPs) were prepared and evaluated for their targeting efficiency and toxicity in vitro and in vivo. The MTX-mPEG-CS NP size determined by dynamic light scattering was 213 ± 2.0 nm with a narrow particle size distribution, and its loading content (LC %) and encapsulation efficiency (EE) were 44.19 ± 0.64% and 87.65 ± 0.79%, respectively. In vitro release behavior of MTX was investigated. In vivo optical imaging in mice proved that MTX was released from particles subsequently and targeted to tumor tissue, showing significantly prolonged retention and specific selectivity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay obviously indicated that the higher inhibition efficiency of MTX-mPEG-CS NPs meant that much more MTX was transferred into the tumor cells. A significant right-shift in the flow cytometry (FCM) assay demonstrated that MTX-loaded nanoparticles were far superior to a pure drug in the inhibition of growth and proliferation of Hela cells. These results suggest that MTX-mPEG-CS NPs could be a promising targeting anticancer chemotherapeutic agent, especially for cervical carcinoma.
机译：癌症纳米疗法正在迅速发展并被实施以解决常规药物输送系统的一些局限性。在本文中，我们报告了一种基于壳聚糖（CS）和甲氧基聚乙二醇（mPEG）的纳米载体制备甲氨蝶呤（MTX）纳米颗粒的新策略，以增强其靶向性和延长血液循环。制备了MTX和mPEG共轭的CS纳米颗粒（NP），并评估了它们在体外和体内的靶向效率和毒性。通过动态光散射测定的MTX-mPEG-CS NP尺寸为213±2.0 nm，粒径分布较窄，其负载量（LC％）和包封效率（EE）为44.19±0.64％和87.65±0.79％，分别。研究了MTX的体外释放行为。小鼠体内光学成像证明，MTX随后从颗粒中释放出来并靶向肿瘤组织，显示出明显延长的保留时间和比选择性。 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物（MTT）测定显然表明MTX-mPEG-CS NP的更高抑制效率意味着更多的MTX被转移到肿瘤细胞中。流式细胞术（FCM）分析中的显着右移表明，载有MTX的纳米颗粒在抑制Hela细胞的生长和增殖方面远远优于纯药物。这些结果表明，MTX-mPEG-CS NPs可能是有前途的靶向抗癌化学治疗剂，尤其是对于宫颈癌。

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