Multifunctional nanospheres for co-delivery of methotrexate and mild hyperthermia to colon cancer cells
Multifunctional nanospheres for co-delivery of methotrexate and mild hyperthermia to colon cancer cells
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DOI：
10.1016/j.msec.2017.03.049
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发表时间：
2017-06-01
影响因子：
7.9
通讯作者：
Duraes, Luisa
中科院分区：
文献类型：
--
作者：
Costa Lima, Sofia A.;Gaspar, Andre;Duraes, Luisa
设计了一种多功能纳米医学平台，并通过基于化疗药物和轻度热疗的组合治疗方法对结肠癌进行有效治疗。甲氨蝶呤（MTX）作为叶酸受体靶向，在肿瘤细胞中过表达，并作为抗癌药物的双重作用的优势。超顺磁性氧化铁纳米颗粒（SPION）的掺入允许通过交变磁场从外部加热癌细胞。开发的纳米载体基于聚乙二醇-聚乳酸（PEG-PLA）纳米球，以改善生物相容性，通过延长血液循环时间来增强其靶向。通过乳化蒸发法制备纳米球，然后对其进行粒径分布、zeta电位、体外药物释放曲线和细胞研究。MTX和SPION在PEG-PLA纳米球上的共递送产生直径为160 nm的尺寸、低于0.2的多分散性指数和约0.5的zeta电位的纳米载体。-18毫伏。多功能纳米球是单分散的，稳定长达3个月。MTX在轻度高温条件下优先释放。与游离药物相比，多功能纳米球能够增加MTX对Caco-2和SW-480结肠癌细胞的细胞毒性。此外，纳米球允许掺入的MTX比游离MTX诱导更大的细胞周期停滞和凋亡效应。这项研究提供的证据表明，MTX-SPION-PEG-PLA纳米球是一种有前途的解决方案，以解决结直肠癌过表达叶酸受体，通过组合的方法。(C)2017 Elsevier B. V.版权所有。
A multifunctional nanomedicine platform was designed and evaluated for efficient colon cancer therapy by a combinatorial therapeutic approach based on a chemotherapeutic drug and mild hyperthermia. Advantage was taken from the dual role of methotrexate (MTX), as folate receptor-targeting, overexpressed in tumor cells, and as anticancer drug. Incorporation of superparamagnetic iron oxide nanoparticles (SPIONs) allows to heat cancer cells externally through an alternating magnetic field. The developed nanocarrier was based on polyethylene glycol-polylactic acid (PEG-PLA) nanospheres to improve biocompatibility, enhancing their targeting by prolonging blood circulation time. By an emulsion-evaporation method the nanospheres were produced and then characterized for size distribution, zeta-potential, in vitro drug release profile and cellular studies. The co-delivery of MTX and SPIONs on PEG-PLA nanospheres resulted in nanocarriers with a size of 160 nm in diameter, a polydispersity index below 0.2 and a zeta potential of ca. -18 mV. Multifunctional nanospheres were monodisperse and stable up to 3 months. MTX was released preferentially under mild hyperthermia conditions. The multifunctional nanospheres were able to increase the cytotoxicity of MTX towards Caco-2 and SW-480 colon cancer cells, in comparison to free drug. Also, the nanospheres allowed the incorporated MTX to induce greater cell cycle arrest and apoptotic effects than the free MTX. This study provides evidences that MTX-SPIONs-PEG-PLA nanospheres are a promising solution to address colorectal cancer over-expressing folate receptors, by a combinatory approach. (C) 2017 Elsevier B.V. All rights reserved.