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用于pH刺激响应型药物递送应用的表面封端介孔二氧化硅纳米颗粒的合成。

Synthesis of surface capped mesoporous silica nanoparticles for pH-stimuli responsive drug delivery applications.

作者信息

Santha Moorthy Madhappan, Bharathiraja Subramanian, Manivasagan Panchanathan, Lee Kang Dae, Oh Junghwan

机构信息

Marine-Integrated Bionics Research Center , Pukyong National University , Busan , 48513 , Republic of Korea . Email:

Department of Otolaryngology-Head and Neck Surgery , Kosin University College of Medicine , Busan 48513 , Republic of Korea.

出版信息

Medchemcomm. 2017 Jul 13;8(9):1797-1805. doi: 10.1039/c7md00270j. eCollection 2017 Sep 1.

Abstract

Mesoporous silica-based drug delivery carriers mostly require appropriate surface modifications to improve their drug delivery efficiency and to reduce their adverse side effects. In the present work, we have synthesised mesoporous silica nanoparticles and their surface was covered by using capping units such as tetrathio-maleimide (TTM) a "host-guest" complexation mechanism for pH-responsive drug delivery applications. The surface-functionalised melamine (Mela) groups on the outer surface of the mesoporous silica nanoparticles act as "hosts" and the surface capped TTM units act as "guests" during the surface capping of the mesoporous silica nanoparticles the "host-guest" complexation approach. After the encapsulation of cargoes into the mesopore channels, the melamine functional groups were covalently immobilised onto the outer surface of the cargo loaded MSNs and then the TTM units were introduced onto the outer surface of the silica nanoparticles as "gatekeepers" to obtain surface capped mesoporous silica (MSN@Mela@TTM/RhB) NPs to protect the loaded cargo molecules inside the mesopore channels and to prevent their premature leakage. The surface-capped TTM units controlled the drug release behavior with respect to the pH of the release medium. In this study, we used rhodamine B (RhB) as a model cargo to study the loading and pH-responsive release behavior of the MSN@Mela@TTM NPs. The encapsulated RhB molecules were retained inside the mesopore channels at physiological pH (pH 7.4) conditions while an enhanced release occurred at acidic pH (pH 5.0 and 4.0) conditions, respectively. Furthermore, the biocompatibility and the intracellular uptake efficiency of the synthesised MSNs@Mela@TTM NPs were examined by using the MDA-MB-231 cell line. The experimental results suggest that the MSNs@Mela@TTM nanoparticles are biocompatible and could be utilised for pH-stimuli responsive drug delivery applications.

摘要

基于介孔二氧化硅的药物递送载体大多需要进行适当的表面修饰,以提高其药物递送效率并减少其不良副作用。在本工作中,我们合成了介孔二氧化硅纳米颗粒,并通过使用诸如四硫代马来酰亚胺(TTM)等封端单元对其表面进行包覆,以用于pH响应型药物递送应用的“主客体”络合机制。在介孔二氧化硅纳米颗粒的表面包覆过程中,介孔二氧化硅纳米颗粒外表面的表面功能化三聚氰胺(Mela)基团充当“主体”,而表面包覆的TTM单元充当“客体”,即“主客体”络合方法。将货物封装到介孔通道中后,将三聚氰胺官能团共价固定在负载货物的介孔二氧化硅纳米颗粒的外表面上,然后将TTM单元作为“守门人”引入到二氧化硅纳米颗粒的外表面上,以获得表面包覆的介孔二氧化硅(MSN@Mela@TTM/RhB)纳米颗粒,以保护介孔通道内负载的货物分子并防止其过早泄漏。表面包覆的TTM单元根据释放介质的pH值控制药物释放行为。在本研究中,我们使用罗丹明B(RhB)作为模型货物来研究MSN@Mela@TTM纳米颗粒的负载和pH响应释放行为。在生理pH(pH 7.4)条件下,封装的RhB分子保留在介孔通道内,而在酸性pH(pH 5.0和4.0)条件下分别发生增强释放。此外,使用MDA-MB-231细胞系检查了合成的MSNs@Mela@TTM纳米颗粒的生物相容性和细胞内摄取效率。实验结果表明,MSNs@Mela@TTM纳米颗粒具有生物相容性,可用于pH刺激响应型药物递送应用。

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