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温度敏感型共聚高分子包覆的荧光介孔硅纳米粒子作为一种活性氧物种激活的药物传递系统。

Temperature-sensitive copolymer-coated fluorescent mesoporous silica nanoparticles as a reactive oxygen species activated drug delivery system.

机构信息

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.

State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.

出版信息

Int J Pharm. 2018 Jan 30;536(1):11-20. doi: 10.1016/j.ijpharm.2017.11.025. Epub 2017 Nov 13.

Abstract

In this study, a temperature and ROS-responsive drug delivery system ROSP@MSN based on mesoporous silica nanoparticles has been designed and synthesized by taking advantage of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acrylate modified polymers (ROSP) as "nano-valve", which can respond selectively to cancer exclusive microenvironment and implement targeted drug release. Due to the superior temperature-sensitive properties of ROSP, ROSP@MSN could achieve cargo loading in cold water, and subsequently close the pore by raising temperature to obtain ROSP@MSN@DOX. Upon the stimulus of ROS, ROSP@MSN@DOX shows good release performance at physiological conditions. The cytotoxicity study demonstrates that the cell viability is about 80% after Hela cells are treated with ROSP@MSN at a concentration of 100 μg/mL for 24 h, exhibiting the good biocompatibility of ROSP@MSN. Furthermore, after treated with ROSP@MSN@DOX at a concentration of 100 μg/mL for 24 h, the viability of Hela cells is reduced to 40.5%; Control experiments demonstrate that, when Hela cells are pretreated with active oxygen scavenger, cell viability is about 65.3% due to the significant decrease of intracellular reactive oxygen species. Therefore, the therapeutic nanocarrier with effective encapsulation and release capacity in particular situation is a great candidate for the new drug delivery platform for targeted cancer therapy.

摘要

在这项研究中,设计并合成了一种基于介孔硅纳米粒子的温度和 ROS 响应型药物输送系统 ROSP@MSN,利用 4-(4,4,5,5-四甲基-1,3,2-二恶硼烷-2-基)苯甲基丙烯酰胺修饰聚合物(ROSP)作为“纳米阀”,该系统可以选择性地响应癌症特有的微环境并实现靶向药物释放。由于 ROSP 的优越温度敏感性,ROSP@MSN 可以在冷水中进行货物装载,然后通过升高温度来关闭孔,从而获得 ROSP@MSN@DOX。在 ROS 的刺激下,ROSP@MSN@DOX 在生理条件下表现出良好的释放性能。细胞毒性研究表明,Hela 细胞在浓度为 100μg/mL 的 ROSP@MSN 处理 24 小时后,细胞活力约为 80%,表明 ROSP@MSN 具有良好的生物相容性。此外,在浓度为 100μg/mL 的 ROSP@MSN@DOX 处理 24 小时后,Hela 细胞的活力降低至 40.5%;对照实验表明,当 Hela 细胞用活性氧清除剂预处理时,由于细胞内活性氧的显著减少,细胞活力约为 65.3%。因此,具有有效封装和特殊情况下释放能力的治疗性纳米载体是用于靶向癌症治疗的新型药物输送平台的理想候选物。

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