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一种新型的温敏性 FeO/聚(甲基丙烯酸甲酯-b-N-异丙基丙烯酰胺-b-丙烯酸)磁性复合纳米球的合成方法及治疗应用。

A new style for synthesis of thermo-responsive FeO/poly (methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) magnetic composite nanosphere and theranostic applications.

机构信息

a Yong Researchers and Elite Club, Jolfa Branch , Islamic Azad University , Jolfa , Iran.

b Department of Chemistry , Payame Noor University , Tehran , Iran.

出版信息

J Biomater Sci Polym Ed. 2017 Dec;28(17):1985-2005. doi: 10.1080/09205063.2017.1364459. Epub 2017 Aug 18.

DOI:10.1080/09205063.2017.1364459
PMID:28783443
Abstract

In this work, a novel thermo-responsive FeO/poly(methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) magnetic composite nanosphere was synthesized for anticancer drug delivery applications. For this propose, the poly(methylmethacrylate-b-N-isopropylacrylamide-b-acrylic acid) [poly (MMA-b-NIPAAm-b-AAc)] was synthesized via reversible addition-fragmentation transfer method. The physic-chemical characterization of the FeO/poly(MMA-b-NIPAAm-b-AAc) magnetic composite nanosphere was investigated by FTIR, HNMR spectroscopies and GPC, FESEM, XRD, VSM and DLS. The thermo-sensitivity of the FeO/P(MMA-b-NIPAAm-b-AAc) magnetic composite nanosphere was confirmed via DLS at 40 °C. DOX encapsulation efficiency was calculated to be 98.2%. The effect of temperature and pH on release behaviors of stimuli responsive DOX-loaded FeO/P(MMA-b-NIPAAm-b-AAc)] magnetic composite nanosphere were investigated. The release rate at pH 7.4, 5.4 and 4 (T = 37 °C) was reached about 24.4, 42.4 and 57.5 wt%, after 4-5 day. The release rate improved at tumor simulated environment (t:40 °C and pH ≤ 5.4). The cytotoxic effects of the magnetic composite nanosphere were appraised by MTT assay and the results indicated that novel developed smart nanocomposite here was nontoxic to MCF-7 cells and can be applied as anti-cancer drug delivery system. Also, the results of the Cellular uptake of MCF7 cells treated with rhodamine labeled DOX-loaded nanocarrier for 2 h have indicated that DOX can be applied as cytotoxic agent and targeting ligand.

摘要

在这项工作中,合成了一种新型的温敏 FeO/聚(甲基丙烯酸甲酯-b-N-异丙基丙烯酰胺-b-丙烯酸)磁性复合纳米球,用于抗癌药物输送应用。为此,通过可逆加成-断裂链转移方法合成了聚(甲基丙烯酸甲酯-b-N-异丙基丙烯酰胺-b-丙烯酸)[聚(MMA-b-NIPAAm-b-AAc)]。通过傅里叶变换红外光谱(FTIR)、HNMR 光谱和凝胶渗透色谱(GPC)、FESEM、XRD、VSM 和 DLS 研究了 FeO/聚(MMA-b-NIPAAm-b-AAc)磁性复合纳米球的物理化学性质。通过在 40°C 下进行 DLS 确认了 FeO/P(MMA-b-NIPAAm-b-AAc)磁性复合纳米球的温敏性。DOX 包封效率计算为 98.2%。研究了温度和 pH 值对刺激响应性 DOX 负载的 FeO/P(MMA-b-NIPAAm-b-AAc)]磁性复合纳米球释放行为的影响。在 pH 值为 7.4、5.4 和 4(T=37°C)下,在 4-5 天后,释放率分别达到约 24.4%、42.4%和 57.5%wt%。在肿瘤模拟环境(t:40°C 和 pH≤5.4)下,释放率提高。通过 MTT 测定评价了磁性复合纳米球的细胞毒性作用,结果表明,新型智能纳米复合材料对 MCF-7 细胞无毒性,可作为抗癌药物输送系统。此外,用 rhodamine 标记的 DOX 负载纳米载体处理 MCF7 细胞 2 小时后的细胞摄取结果表明,DOX 可作为细胞毒性剂和靶向配体。

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