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将疏水性抗癌药物预载入多功能纳米载体用于多模态成像、近红外响应性药物释放及协同治疗

Preloading of Hydrophobic Anticancer Drug into Multifunctional Nanocarrier for Multimodal Imaging, NIR-Responsive Drug Release, and Synergistic Therapy.

作者信息

Wang Hui, Wang Kui, Tian Bowei, Revia Richard, Mu Qingxin, Jeon Mike, Chang Fei-Chien, Zhang Miqin

机构信息

Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA.

Department of Applied Mathematics, University of Washington, Seattle, WA, 98195, USA.

出版信息

Small. 2016 Dec;12(46):6388-6397. doi: 10.1002/smll.201602263. Epub 2016 Sep 27.

Abstract

Applications of hydrophobic drug-based nanocarriers (NCs) remain largely limited because of their low loading capacity. Here, development of a multifunctional hybrid NC made of a magnetic Fe3O4 core and a mesoporous silica shell embedded with carbon dots (CDs) and paclitaxel (PTX), and covered by another layer of silica is reported. The NC is prepared via a one-pot process under mild condition. The PTX loading method introduced in this study simplifies drug loading process and demonstrates a high loading capacity due to mesoporous silica dual-shell structure, supramolecular π-stacking between conjugated rings of PTX molecules, and aromatic rings of the CDs in the hybrid NC. The CDs serve as both confocal and two-photon fluorescence imaging probes, while the Fe3O4 core serves as a magnetic resonance imaging contrast agent. Significantly, NC releases PTX in response to near infrared irradiation as a result of local heating of the embedded CDs and the heating of CDs also provides an additional therapeutic effect by thermally killing cancer cells in tumor in addition to the chemotherapeutic effect of released PTX. Both in vitro and in vivo results show that NC demonstrates high therapeutic efficacy through a synergistic effect from the combined chemo-photothermal treatments.

摘要

基于疏水性药物的纳米载体(NCs)的应用由于其低载药量而在很大程度上受到限制。在此,报道了一种多功能杂化纳米载体的研发,该纳米载体由磁性Fe3O4核和包裹有碳点(CDs)与紫杉醇(PTX)的介孔二氧化硅壳层组成,并被另一层二氧化硅覆盖。该纳米载体是在温和条件下通过一锅法制备的。本研究中引入的PTX载药方法简化了载药过程,并且由于介孔二氧化硅双壳结构、杂化纳米载体中PTX分子共轭环与CDs芳环之间的超分子π-堆积作用而展现出高载药量。碳点同时用作共聚焦和双光子荧光成像探针,而Fe3O4核用作磁共振成像造影剂。值得注意的是,由于嵌入的碳点的局部加热,纳米载体在近红外照射下释放PTX,并且碳点的加热除了释放的PTX的化疗作用外,还通过热杀死肿瘤中的癌细胞提供额外的治疗效果。体外和体内结果均表明,纳米载体通过联合化疗-光热治疗的协同作用展现出高治疗效果。

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