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基于外泌体功能化氧化石墨烯的复合仿生智能药物递送系统的构建及其抗癌活性。

Construction of an exosome-functionalized graphene oxide based composite bionic smart drug delivery system and its anticancer activity.

机构信息

College of Life Sciences, Qufu Normal University, Qufu 273165, Shandong, People's Republic of China.

出版信息

Nanotechnology. 2022 Feb 1;33(17). doi: 10.1088/1361-6528/ac49bf.

Abstract

Graphene oxide has covalently modified by chito oligosaccharides and-polyglutamic acid to form GO-CO--PGA, which exhibits excellent performance as a drug delivery carrier, but this carrier did not have the ability to actively target. In this study, the targeting property of breast cancer tumor cell exosomes was exploited to give GO-CO--PGA the ability to target breast tumor cells (MDA-MB-231), and the drug mitoxantrone (MIT) was loaded to finally form EXO-GO-CO--PGA-MIT with an encapsulation efficiency of 73.02%. The pH response of EXO-GO-CO--PGA showed a maximum cumulative release rate of 56.59% (pH 5.0, 120 h) and 6.73% (pH 7.4, 120 h) for MIT at different pH conditions.cellular assays showed that EXO-GO-CO--PGA-MIT was more potent in killing MDA-MB-231 cells due to its targeting ability and had a significantly higher pro-apoptotic capacity compared to GO-CO--PGA-MIT. The results showed that this bionic nano-intelligent drug delivery system has good drug slow release function and it can increase the local drug concentration of tumor and enhance the pro-apoptotic ability of MIT, so this newly synthesized bionic drug delivery carriers (EXO-GO-CO--PGA-MIT) has potential application in breast cancer treatment.

摘要

氧化石墨烯被壳寡糖和聚谷氨酸共价修饰,形成 GO-CO--PGA,作为药物载体具有优异的性能,但这种载体没有主动靶向的能力。本研究利用乳腺癌肿瘤细胞外泌体的靶向特性,赋予 GO-CO--PGA 靶向乳腺癌细胞(MDA-MB-231)的能力,并负载米托蒽醌(MIT),最终形成包封率为 73.02%的 EXO-GO-CO--PGA-MIT。EXO-GO-CO--PGA 的 pH 响应在不同 pH 条件下,MIT 的最大累积释放率分别为 56.59%(pH 5.0,120 h)和 6.73%(pH 7.4,120 h)。细胞实验表明,由于其靶向能力,EXO-GO-CO--PGA-MIT 对 MDA-MB-231 细胞的杀伤作用更强,与 GO-CO--PGA-MIT 相比,具有更高的促凋亡能力。结果表明,这种仿生纳米智能药物传递系统具有良好的药物缓释功能,能够增加肿瘤局部药物浓度,增强 MIT 的促凋亡能力,因此,这种新合成的仿生药物载体(EXO-GO-CO--PGA-MIT)在乳腺癌治疗中具有潜在的应用价值。

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