H ₂ O ₂ -responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay

Abstract

Abnormal H 2 O 2 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 H 2 O 2 -responsive chromogenic assay with great specificity and sensitivity. In the presence of H 2 O 2 , colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared (NIR) absorbance, enabling photoacoustic detection of H 2 O 2 down to submicromolar concentrations. Using Lipo@HRP&ABTS as an H 2 O 2 -responsive nanoprobe, we could accurately detect the inflammation processes induced by LPS or bacterial infection in which H 2 O 2 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 H 2 O 2 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 H 2 O 2 contents. Moreover, using the H 2 O 2 -dependent strong NIR absorbance of Lipo@HRP&ABTS, tumorspecific photothermal therapy is also achieved. This work thus develops a sensitive H 2 O 2 -responsive optical nanoprobe useful not only for in vivo detection of inflammation but also for tumor-specific theranostic applications.hydrogen peroxide | inflammation | tumor | photoacoustic imaging | photothermal therapy

Tumor Microenvironment Adaptable Nanoplatform for O2 Self‐Sufficient Chemo/Photodynamic Combination Therapy

“…The overexpression of H 2 O 2 is a typical feature of tumorigenesis and progression,44–46 which provided favorable conditions for PMDH to relieve tumor hypoxia by producing O 2 . To evaluate this process, colorectal cancer (CT26) cells were chosen to incubate with PMDH for confocal laser scanning microscopy (CLSM) observations by using hypoxia stress detection kit.…”

Photoacoustic Probes for Molecular Detection: Recent Advances and Perspectives

“…: Recently, Liu and co‐workers used hydrophilic HRP protein and its substrate 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) to obtain a H 2 O 2 ‐responsive PA nanoprobe (denoted as Lipo@HRP&ABTS) . The ABTS was the active component, which had no PA signal within the NIR region.…”

“…d) Schematic illustration showing PA imaging of LPS‐induced for in vivo inflammation with Lipo@HRP&. Reproduced with permission . Copyright 2017, National Academy of Sciences.…”

Er3+ Sensitized 1530 nm to 1180 nm Second Near‐Infrared Window Upconversion Nanocrystals for In Vivo Biosensing

“…In stark contrast with stable luminescence of the 1180 nm channel (Figure 5D), the signal of 980 nm channel was gradually increased as evolution of the inflammation because of the continuously generating of H 2 O 2 ( Figure 5C). [11] In summary,E r 3+ sensitized NaErF 4 :Ln 3+ @NaYF 4 UCNPs (Ln 3+ = Ho 3+ or Nd 3+ )w ere synthesized for the first time.T he NIR-II upconversion emissions with large anti-Stokes shifting of Er 3+ (980 nm), Ho 3+ (1180 nm) and Nd 3+ (1060 nm) can be achieved by the well-designed core-shell structure,o ptimized the doping concentration and the shell layer thickness under the 1530 nm irradiation. [11] In summary,E r 3+ sensitized NaErF 4 :Ln 3+ @NaYF 4 UCNPs (Ln 3+ = Ho 3+ or Nd 3+ )w ere synthesized for the first time.T he NIR-II upconversion emissions with large anti-Stokes shifting of Er 3+ (980 nm), Ho 3+ (1180 nm) and Nd 3+ (1060 nm) can be achieved by the well-designed core-shell structure,o ptimized the doping concentration and the shell layer thickness under the 1530 nm irradiation.…”