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快速制备碳量子点作为用于双模态靶向成像和化疗的多功能纳米载体。

Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual-modal targeted imaging and chemotherapy.

作者信息

Chiu Sheng-Hui, Gedda Gangaraju, Girma Wubshet Mekonnen, Chen Jem-Kun, Ling Yong-Chien, Ghule Anil V, Ou Keng-Liang, Chang Jia-Yaw

机构信息

Department of Chemical Engineering, National Taiwan University of Science and Technology, 43, Section 4, Keelung Road, Taipei 10607, Taiwan.

Department of Materials Science and Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan.

出版信息

Acta Biomater. 2016 Dec;46:151-164. doi: 10.1016/j.actbio.2016.09.027. Epub 2016 Sep 20.

Abstract

UNLABELLED

Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of FA-GdNS@CQDs. FA-GdNS@CQDs enhanced the MR response as compared to that for commercial Gd-DTPA. The targeting capabilities of FA-GdNS@CQDs were confirmed in HeLa and HepG2 cells using in vitro fluorescence and MR dual modality imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the FA-GdNS@CQDs forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. Importantly, the prepared FA-GdNS@CQDs-DOX showed a high quantity of doxorubicin loading capacity (about 80%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the FA-GdNS@CQDs were observed by confocal laser scanning microscopy. We also successfully demonstrated in vivo fluorescence bio imaging of the FA-GdNS@CQDs, using zebrafish as an animal model.

STATEMENT OF SIGNIFICANCE

In this manuscript, we reported a facial, rapid, and environmental friendly method to fabricate hetero atoms including gadolinium, nitrogen, and sulfur doped multi-functional magnetofluorescent carbon quantum dots (GdNS@CQDs) nanocomposite. These multifunctional GdNS@CQDs were conjugated with a folic acid for targeting dual modal fluorescence/magnetic resonance imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the nanocomposite forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. We have developed GdNS@CQDs with integrated functions for simultaneous in vitro cell imaging, targeting, and pH-sensitive controlled drug release in HeLa cells. Furthermore, we successfully demonstrated the use of this material for in vivo fluorescence imaging, using zebrafish as an animal model.

摘要

未标注

在此,我们通过一锅法微波法在10分钟内合成了一种硫、氮和钆三元素掺杂的磁荧光碳量子点(GdNS@CQDs)。我们的结果表明,这些磁荧光GdNS@CQDs具有优异的荧光和磁性。此外,GdNS@CQDs在生理条件和离子强度下表现出高稳定性。这些磁荧光GdNS@CQDs与叶酸偶联,记为FA-GdNS@CQDs,用于靶向双模态荧光/磁共振(MR)成像。体外和体内研究证实了FA-GdNS@CQDs具有高生物相容性和低毒性。与市售钆喷酸葡胺相比,FA-GdNS@CQDs增强了MR响应。使用体外荧光和MR双模态成像在HeLa和HepG2细胞中证实了FA-GdNS@CQDs的靶向能力。此外,将抗癌药物阿霉素掺入FA-GdNS@CQDs中形成FA-GdNS@CQDs-DOX,实现靶向给药。重要的是,制备的FA-GdNS@CQDs-DOX显示出高阿霉素负载量(约80%)和pH敏感药物释放。通过共聚焦激光扫描显微镜观察了FA-GdNS@CQDs对癌细胞的摄取和细胞内定位。我们还以斑马鱼为动物模型成功地证明了FA-GdNS@CQDs的体内荧光生物成像效果。

意义声明

在本论文中,我们报道了一种简便、快速且环境友好的方法来制备包含钆、氮和硫掺杂的多功能磁荧光碳量子点(GdNS@CQDs)纳米复合材料。这些多功能GdNS@CQDs与叶酸偶联用于靶向双模态荧光/磁共振成像。此外,将抗癌药物阿霉素掺入纳米复合材料中形成FA-GdNS@CQDs-DOX,实现靶向给药。我们开发了具有集成功能的GdNS@CQDs用于HeLa细胞中的体外细胞成像、靶向和pH敏感的控释。此外,我们以斑马鱼为动物模型成功地证明了该材料用于体内荧光成像的效果。

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