Enhanced in vitro antitumor efficacy of a polyunsaturated fatty acid-conjugated pH-responsive self-assembled ion-pairing liposome-encapsulated prodrug.

IF 2.8 4区 材料科学 Q3 MATERIALS SCIENCE, MULTIDISCIPLINARY
Nanotechnology Pub Date : 2020-04-10 Epub Date: 2019-12-17 DOI:10.1088/1361-6528/ab62d1
Yuxian Wang, Panpan Fan, Liying Zhu, Wei Zhuang, Ling Jiang, Hongman Zhang, He Huang
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引用次数: 6

Abstract

The development of clinical chemotherapeutics is always challenging due to the toxicity and side effects of drugs not only for tumor cells but also for normal cells. Therefore, nano-drug delivery systems and prodrug strategies have been applied to address this challenge. Herein, we report a liposome-encapsulated small-molecule prodrug nanosystem, self-assembled by doxorubicin (DOX) and mixed polyunsaturated fatty acid (MPUFA) ion-pairing (MPUFAs-DOX@Liposomes), which has a high omega-3 PUFA content. The increased lipophilicity of ion-paired MPUFAs-DOX can significantly improve the drug loading efficiency (∼97%). Electrostatic interaction, the hydrophobic effect and hydrogen bonding between the ion-pairing agents led to superior pH-responsive release of DOX from liposomes over DOX-loaded liposomes (DOX@Liposomes), with a more rapid release rate at pH 5.0 than at pH 7.4, which is beneficial for decreasing the toxicity of DOX under physiological conditions. Finally, the in vitro antitumor effects were investigated for two tumor cell types, A549 and MCF-7, and the results demonstrated that MPUFAs-DOX@Liposomes showed the highest cytotoxicity compared with free DOX and DOX@Liposomes because of the ready uptake under the effect of PUFAs. Hence, liposomes loaded with ion-paired MPUFAs-DOX is a promising formulation for combination cancer therapy.

多不饱和脂肪酸偶联ph响应型自组装离子配对脂质体包封前药体外抗肿瘤效果的研究。
由于药物不仅对肿瘤细胞而且对正常细胞具有毒副作用,临床化疗的发展一直具有挑战性。因此,纳米药物递送系统和前药策略已被应用于解决这一挑战。在此,我们报道了一种脂质体封装的小分子前药纳米系统,该系统由阿霉素(DOX)和混合多不饱和脂肪酸(MPUFA)离子配对自组装(MPUFAs-DOX@Liposomes),具有高omega-3 PUFA含量。离子配对MPUFAs-DOX的亲脂性增加可以显著提高载药效率(约97%)。离子配对剂之间的静电相互作用、疏水效应和氢键作用导致脂质体中DOX的pH响应性优于负载DOX的脂质体(DOX@Liposomes), pH 5.0时的释放速度比pH 7.4时更快,这有利于降低生理条件下DOX的毒性。最后,研究了A549和MCF-7两种肿瘤细胞的体外抗肿瘤作用,结果表明MPUFAs-DOX@Liposomes与游离DOX和DOX@Liposomes相比,具有最高的细胞毒性,这是由于在PUFAs的作用下,MPUFAs-DOX@Liposomes可被迅速摄取。因此,负载离子配对MPUFAs-DOX的脂质体是一种很有前途的联合癌症治疗制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nanotechnology
Nanotechnology 工程技术-材料科学:综合
CiteScore
7.10
自引率
5.70%
发文量
820
审稿时长
2.5 months
期刊介绍: The journal aims to publish papers at the forefront of nanoscale science and technology and especially those of an interdisciplinary nature. Here, nanotechnology is taken to include the ability to individually address, control, and modify structures, materials and devices with nanometre precision, and the synthesis of such structures into systems of micro- and macroscopic dimensions such as MEMS based devices. It encompasses the understanding of the fundamental physics, chemistry, biology and technology of nanometre-scale objects and how such objects can be used in the areas of computation, sensors, nanostructured materials and nano-biotechnology.
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