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磁响应纳米载体用于癌症治疗中 pH 响应性阿霉素释放。

Magnetic Driven Nanocarriers for pH-Responsive Doxorubicin Release in Cancer Therapy.

机构信息

CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal.

CICECO-Aveiro Institute of Materials, Department of Physics, University of Aveiro, 3810-193 Aveiro, Portugal.

出版信息

Molecules. 2020 Jan 14;25(2):333. doi: 10.3390/molecules25020333.

Abstract

Doxorubicin is one of the most widely used anti-cancer drugs, but side effects and selectivity problems create a demand for alternative drug delivery systems. Herein we describe a hybrid magnetic nanomaterial as a pH-dependent doxorubicin release carrier. This nanocarrier comprises magnetic iron oxide cores with a diameter of 10 nm, enveloped in a hybrid material made of siliceous shells and ĸ-carrageenan. The hybrid shells possess high drug loading capacity and a favorable drug release profile, while the iron oxide cores allows easy manipulation via an external magnetic field. The pH responsiveness was assessed in phosphate buffers at pH levels equivalent to those of blood (pH 7.4) and tumor microenvironment (pH 4.2 and 5). The nanoparticles have a loading capacity of up to 12.3 wt.% and a release profile of 80% in 5 h at acidic pH versus 25% at blood pH. In vitro drug delivery tests on human breast cancer and non-cancer cellular cultures have shown that, compared to the free drug, the loaded nanocarriers have comparable antiproliferative effect but a less intense cytotoxic effect, especially in the non-cancer cell line. The results show a clear potential for these new hybrid nanomaterials as alternative drug carriers for doxorubicin.

摘要

多柔比星是最广泛使用的抗癌药物之一,但副作用和选择性问题导致人们对替代药物输送系统的需求。在此,我们描述了一种作为 pH 依赖性多柔比星释放载体的混合磁性纳米材料。该纳米载体由直径为 10nm 的磁性氧化铁核组成,被由硅壳和 κ-卡拉胶组成的混合材料包裹。混合壳具有高载药能力和有利的药物释放特性,而氧化铁核允许通过外部磁场进行轻松操作。在磷酸盐缓冲液中评估了 pH 响应性,缓冲液的 pH 值相当于血液(pH7.4)和肿瘤微环境(pH4.2 和 5)的 pH 值。纳米颗粒的载药能力高达 12.3wt.%,在酸性 pH 下 5 小时的释放率为 80%,而在血液 pH 下为 25%。在人乳腺癌和非癌细胞培养物上的体外药物输送测试表明,与游离药物相比,负载的纳米载体具有相当的抗增殖作用,但细胞毒性作用较弱,尤其是在非癌细胞系中。结果表明,这些新型混合纳米材料作为多柔比星的替代药物载体具有明显的潜力。

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