Department of Nanomedicine and Biopharmaceuticals, College of Life Science and Technology , Huazhong University of Science and Technology , Wuhan 430074 , China.
National Engineering Research Center for Nanomedicine , Huazhong University of Science and Technology , Wuhan 430074 , China.
Nano Lett. 2019 Aug 14;19(8):5806-5817. doi: 10.1021/acs.nanolett.9b02769. Epub 2019 Jul 24.
Constructing a tumor microenvironment stimuli activatable theranostic nanoparticle with simple components and preparation procedures for multimodality imaging and therapy remains a major challenge for current theranostic systems. Here we report a novel and simple glutathione (GSH)-responsive turn-on theranostic nanoparticle for dual-modal imaging and combination therapy. The theranostic nanoparticle, DHP, consisting of a disulfide-bond-linked hydroxyethyl starch paclitaxel conjugate (HES-SS-PTX) and a near-infrared (NIR) cyanine fluorophore DiR, is prepared with a simple one-step dialysis method. As DiR is encapsulated within the hydrophobic core formed by HES-SS-PTX, the fluorescence of DiR is quenched by the aggregation-caused quenching (ACQ) effect. Nonetheless, once DHP is internalized by cancer cells, the disulfide bond of HES-SS-PTX can be cleaved by intracellular GSH, leading to the synchronized release of conjugated PTX and loaded DiR. The released PTX could exert its therapeutic effect, while DiR could adsorb onto nearby endosome/lysosome membranes and regain its fluorescence. Thus, DHP could monitor the release and therapeutic effect of PTX through the fluorescence recovery of DiR. Remarkably, DHP can also be used as an probe for both fluorescent and photoacoustic imaging and at the same time achieves potent antitumor efficacy through chemo-photothermal combination therapy. This study provides novel insights into designing clinically translatable turn-on theranostic systems.
构建一种具有简单组成和制备程序的肿瘤微环境刺激激活治疗性纳米粒子，用于多模态成像和治疗，仍然是当前治疗系统的主要挑战。在这里，我们报告了一种新型的、简单的谷胱甘肽（GSH）响应型开启治疗性纳米粒子，用于双模态成像和联合治疗。治疗性纳米粒子 DHP 由二硫键连接的羟乙基淀粉紫杉醇偶联物（HES-SS-PTX）和近红外（NIR）菁染料 DiR 组成，采用简单的一步透析法制备。由于 DiR 被包裹在由 HES-SS-PTX 形成的疏水性核心内，DiR 的荧光被聚集诱导猝灭（ACQ）效应猝灭。然而，一旦 DHP 被癌细胞内化，HES-SS-PTX 的二硫键就会被细胞内的 GSH 切断，导致共轭 PTX 和负载的 DiR 同步释放。释放的 PTX 可以发挥其治疗作用，而 DiR 可以吸附在附近的内体/溶酶体膜上并恢复其荧光。因此，DHP 可以通过 DiR 的荧光恢复来监测 PTX 的释放和治疗效果。值得注意的是，DHP 还可以用作荧光和光声成像的探针，同时通过化学-光热联合治疗实现有效的抗肿瘤疗效。本研究为设计临床可转化的开启治疗性系统提供了新的思路。
