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氯乙啶 6 和聚多巴胺修饰的金纳米花用于联合光热和光动力治疗。

Chlorin e6 and polydopamine modified gold nanoflowers for combined photothermal and photodynamic therapy.

机构信息

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 20040, China.

Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, 20040, China.

出版信息

J Mater Chem B. 2020 Mar 11;8(10):2128-2138. doi: 10.1039/c9tb02646k.

Abstract

Combinational photo-based approaches with enhanced efficacy for cancer therapy have garnered increasing attention in recent years. In this work, a multifunctional system for synergistic photothermal and photodynamic cancer therapy was successfully prepared. The system consists of gold nanoflowers (AuNFs) conjugated with Chlorin e6 (Ce6), and then coated with a polydopamine (PDA) layer. AuNFs with diameters around 80 nm and a broad absorbance in the visible-near infrared (Vis-NIR) range of 500 to 800 nm, were successfully synthesized by a two-step process at 0 °C, using HAuCl4, ascorbic acid (AA), and hydroxylamine hydrochloride (NH2OH·HCl) as the reactants. Glutathione (GSH) molecules chemically anchored to the gold surfaces were used to provide addressable sites for Ce6 conjugated to GSH-AuNFs through an amidation reaction. A PDA layer was then wrapped outside the Ce6-GSH-AuNFs via self-polymerization of dopamine, which provided additional chemical modification and functionalization. Finally, the multifunctional PDA-Ce6-GSH-AuNFs were obtained. The content of Ce6 incorporated into the AuNFs was 14.0 wt%, and the singlet oxygen yield of PDA-Ce6-GSH-AuNFs was approximately 91.0% of that of free Ce6. PDA-Ce6-GSH-AuNFs showed better photothermal conversion efficiency (η = 23.6%), lower cytotoxicity, and faster cell internalization. Both in vitro and in vivo investigation of the combined treatment with a near-infrared (NIR) laser (660 nm for photodynamic therapy, and 808 nm for photothermal therapy) demonstrated that PDA-Ce6-GSH-AuNFs had excellent phototoxicity and synergistic effects of killing cancer cells. Hence, PDA-Ce6-GSH-AuNFs are a dual phototherapeutic agent that exhibits photodynamic and photothermal therapeutic effects and has potential application in enhanced cancer therapy.

摘要

近年来,基于组合的光疗方法与增强疗效的癌症治疗策略受到了越来越多的关注。在这项工作中,成功制备了一种用于协同光热和光动力癌症治疗的多功能系统。该系统由金纳米花(AuNFs)与氯乙锭(Ce6)偶联,然后涂覆一层聚多巴胺(PDA)层。通过两步法在 0°C 下成功合成了直径约 80nm、在 500-800nm 可见光-近红外(Vis-NIR)范围内具有宽吸收的 AuNFs,使用 HAuCl4、抗坏血酸(AA)和盐酸羟胺(NH2OH·HCl)作为反应物。通过酰胺化反应,将化学锚定在金表面上的谷胱甘肽(GSH)分子用于提供与 GSH-AuNFs 偶联的 Ce6 的可寻址位点。然后通过多巴胺的自聚合将一层 PDA 包裹在 Ce6-GSH-AuNFs 外部,这提供了额外的化学修饰和功能化。最后,得到了多功能的 PDA-Ce6-GSH-AuNFs。AuNFs 中掺入的 Ce6 含量为 14.0wt%,PDA-Ce6-GSH-AuNFs 的单线态氧产率约为游离 Ce6 的 91.0%。PDA-Ce6-GSH-AuNFs 表现出更好的光热转换效率(η=23.6%)、更低的细胞毒性和更快的细胞内化。近红外(NIR)激光(用于光动力治疗的 660nm 和用于光热治疗的 808nm)的体外和体内联合治疗研究表明,PDA-Ce6-GSH-AuNFs 具有优异的光毒性和协同杀伤癌细胞的效果。因此,PDA-Ce6-GSH-AuNFs 是一种双重光疗剂,具有光动力和光热治疗效果,在增强癌症治疗方面具有潜在的应用。

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