H₂O₂-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 114; no. 21; pp. 5343 - 5348
• Main Authors: Chen, Qian, Liang, Chao, Sun, Xiaoqi, Chen, Jiawen, Yang, Zhijuan, Zhao, He, Feng, Liangzhu, Liu, Zhuang
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences 23.05.2017
• Subjects: Biological Sciences; Physical Sciences
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1701976114

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.