Multifunctional mesoporous nanoparticles as pH-responsive Fe2+ reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth

Multifunctional mesoporous nanoparticles as pH-responsive Fe2+ reservoirs and artemisinin vehicles for synergistic inhibition of tumor growth
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多功能介孔纳米颗粒作为 pH 响应型 Fe2+ 储库和青蒿素载体,协同抑制肿瘤生长

DOI:
10.1016/j.biomaterials.2014.04.028
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发表时间:
2014-08-01
期刊:
影响因子:
14
通讯作者:
Chen, Qian-Wang
Chen, Qian-Wang
中科院分区:
工程技术1区
文献类型:
--
作者:
Chen, Jian;Guo, Zhen;Chen, Qian-Wang

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青蒿素(ART)是一种铁依赖性抗癌药物。然而,将疏水ART和Fe2+离子同时递送到癌细胞中仍然是一个主要的挑战。在此,我们报道了Fe3O4@C/Ag@mSiO(2) (FCA@mSiO(2))多功能纳米载体,其可负载高达484 mg/g的ART。此外,FCA@InSiO2纳米颗粒具有ph响应性,在FCA@mSiO(2)纳米颗粒培养的HeLa细胞中,Fe2+离子浓度可达2.765 nmol/L。与游离ART相比,MU法检测的载ART FCA@mSiO(2)纳米颗粒的抗肿瘤效果显著增强。结果表明,负载ART的FCA@InSiO2纳米颗粒被HeLa细胞内化,位于核内体和溶酶体的酸性腔室中,释放Fe2+离子,将ART非酶转化为毒性产物,杀死癌细胞。这一结果为利用天然药物进行抗癌治疗提供了一条新的途径。(C) 2014 Elsevier Ltd.版权所有。
Artemisinin (ART) is an iron-dependent anti-cancer drug. However, simultaneous delivery of hydrophobic ART and Fe2+ ions into cancer cells remains a major challenge. Herein, we reported Fe3O4@C/Ag@mSiO(2) (FCA@mSiO(2)) multifunctional nanocarriers which can load ART as high as 484 mg/g. Moreover, FCA@InSiO2 nanoparticles demonstrated pH-responsive Fe2+ release, the concentration of Fe2+ ions can reach 2.765 nmol/L in HeLa cells cultured with FCA@mSiO(2) nanoparticles. The antitumor efficacy of ART-loaded FCA@mSiO(2) nanoparticles measured by MU assay was significantly enhanced compared with free ART. It was suggested that the ART-loaded FCA@InSiO2 nanoparticles are internalized by HeLa cells and located at the acidic compartments of endosomes and lysosomes, releasing Fe2+ ions to non-enzymatically convert ART to toxic products for killing cancer cells. This result provides a way for using promising natural drugs in anti-cancer therapeutics. (C) 2014 Elsevier Ltd. All rights reserved.