Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release
Intelligent Janus nanoparticles for intracellular real-time monitoring of dual drug release
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智能Janus纳米颗粒用于细胞内实时监测双重药物释放
DOI：
10.1039/c6nr00987e
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发表时间：
2016-01-01
期刊：
影响因子：
6.7
通讯作者：
Shao, Zhengzhong
中科院分区：
文献类型：
--
作者：
Cao, Han;Yang, Yuhong;Shao, Zhengzhong
刺激响应性纳米材料作为药物递送载体受到了广泛关注，然而，了解载体中的多种药物释放以实现有效的治疗是非常具有挑战性的。在这里，我们报道了一种新型纳米系统，Janus粒子Dox-CMR-MS/Au-6MP（Dox：阿霉素，CMR：7-羟基香豆素-3-羧酸酯，MS：介孔二氧化硅，Au：金，6MP：6-巯基嘌呤），具有相反的MS和Au面，可以基于荧光共振能量转移（FRET）实时监测细胞内双药（Dox和6MP）控释和表面增强拉曼散射（SERS）。 FRET 受体 Dox 通过 pH 响应连接体腙连接到 CMR（作为 FRET 供体）缀合的 MS，6MP 通过金-硫醇相互作用缀合到 Au 表面。当Janus纳米颗粒进入肿瘤细胞时，酸性环境中腙键的断裂和癌细胞中过表达的谷胱甘肽（GSH）的取代分别导致Dox和6MP的释放。因此，CMR荧光信号的变化和6MP的SERS降低可用于实时监测活细胞内双药的释放。此外，这项工作证明了设计的双载药纳米系统增强的抗癌作用。因此，当前的研究可能为智能多药递送和释放以及细胞对药物治疗的反应的实时研究提供新的视角。
Stimuli-responsive nanomaterials have been receiving much attention as drug delivery carriers, however understanding of multi-drug release from the carriers for efficient therapeutics is highly challenging. Here, we report a novel nanosystem, Janus particle Dox-CMR-MS/Au-6MP (Dox: doxorubicin, CMR: 7-hydroxycoumarin-3-carboxylate, MS: mesoporous silica, Au: gold, 6MP: 6-mercaptopurine) with opposing MS and Au faces, which can monitor intracellular dual-drug (Dox and 6MP) controlled release in real time based on fluorescence resonance energy transfer (FRET) and surface-enhanced Raman scattering (SERS). The FRET acceptor Dox is attached to CMR (as a FRET donor) conjugated MS with a pH-responsive linker hydrazone, and 6MP is conjugated to the Au surface through the gold-thiol interaction. As the Janus nanoparticle enters into tumor cells, the breakage of the hydrazone bond in an acidic environment and the substitution of glutathione (GSH) overexpressed in cancer cells give rise to the release of Dox and 6MP, respectively. Thus, the change of the CMR fluorescence signal and the SERS decrease of 6MP can be used to monitor the dual-drug release within living cells in real time. In addition, this work demonstrates the enhanced anticancer effect of the designed dual-drug loaded nanosystem. Therefore, the current study may provide new perspectives for the real-time study of intelligent multidrug delivery and release, as well as cellular responses to drug treatment.