Abnormal H2O2 levels are closely related to many diseases, including inflammation and cancers. Herein, we simultaneously load HRP and its substrate, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), into liposomal nanoparticles, obtaining a Lipo@HRP&ABTS optical nanoprobe for in vivo H2O2-responsive chromogenic assay with great specificity and sensitivity. In the presence of H2O2, colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared (NIR) absorbance, enabling photoacoustic detection of H2O2 down to submicromolar concentrations. Using Lipo@HRP&ABTS as an H2O2-responsive nanoprobe, we could accurately detect the inflammation processes induced by LPS or bacterial infection in which H2O2 is generated. Meanwhile, upon systemic administration of this nanoprobe we realize in vivo photoacoustic imaging of small s.c. tumors (∼2 mm in size) as well as orthotopic brain gliomas, by detecting H2O2 produced by tumor cells. Interestingly, local injection of Lipo@HRP&ABTS further enables differentiation of metastatic lymph nodes from those nonmetastatic ones, based on their difference in H2O2 contents. Moreover, using the H2O2-dependent strong NIR absorbance of Lipo@HRP&ABTS, tumor-specific photothermal therapy is also achieved. This work thus develops a sensitive H2O2-responsive optical nanoprobe useful not only for in vivo detection of inflammation but also for tumor-specific theranostic applications.

译文

H2O2水平异常与许多疾病密切相关,包括炎症和癌症。在本文中,我们同时将HRP及其底物2,2 '-叠氮基-双 (3-乙基苯并噻唑啉-6-磺酸) (ABTS) 加载到脂质体纳米颗粒中,获得Lipo @ HRP & ABTS光学纳米探针,用于具有高度特异性和灵敏度的体内H2O2-responsive显色测定。在存在H2O2的情况下,HRP会将无色ABTS转化为具有强近红外 (NIR) 吸光度的氧化形式,从而能够将H2O2的光声检测降至亚微摩尔浓度。使用Lipo @ HRP & ABTS作为H2O2-responsive纳米探针,我们可以准确地检测由LPS或细菌感染引起的H2O2引起的炎症过程。同时,在系统施用该纳米探针后,我们实现了小s.C.的体内光声成像。通过检测肿瘤细胞产生的H2O2,肿瘤 (约2毫米大小) 以及原位脑胶质瘤。有趣的是,根据H2O2含量的差异,局部注射Lipo @ HRP和ABTS进一步使转移淋巴结与非转移淋巴结区分。此外,使用Lipo @ HRP & ABTS H2O2-dependent强的NIR吸光度,还可以实现肿瘤特异性光热治疗。因此,这项工作开发了一种灵敏的H2O2-responsive光学纳米探针,不仅可用于体内检测炎症,而且可用于肿瘤特异性治疗应用。

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