A H2O2-activatable nanoprobe for diagnosing interstitial cystitis and liver ischemia-reperfusion injury via multispectral optoacoustic tomography and NIR-II fluorescent imaging

Abstract

Developing high-quality NIR-II fluorophores (emission in 1000–1700 nm) for in vivo imaging is of great significance. Benzothiadiazole-core fluorophores are an important class of NIR-II dyes, yet ongoing limitations such as aggregation-caused quenching in aqueous milieu and non-activatable response are still major obstacles for their biological applications. Here, we devise an activatable nanoprobe to address these limitations. A molecular probe named BTPE-NO2 is synthesized by linking a benzothiadiazole core with two tetraphenylene groups serving as hydrophobic molecular rotors, followed by incorporating two nitrophenyloxoacetamide units at both ends of the core as recognition moieties and fluorescence quenchers. An FDA-approved amphiphilic polymer Pluronic F127 is then employed to encapsulate the molecular BTPE-NO2 to render the nanoprobe BTPE-NO2@F127. The pathological levels of H2O2 in the disease sites cleave the nitrophenyloxoacetamide groups and activate the probe, thereby generating strong fluorescent emission (950~1200 nm) and ultrasound signal for multi-mode imaging of inflammatory diseases. The nanoprobe can therefore function as a robust tool for detecting and imaging the disease sites with NIR-II fluorescent and multispectral optoacoustic tomography (MSOT) imaging. Moreover, the three-dimensional MSOT images can be obtained for visualizing and locating the disease foci.

Reactive Species-Activatable AIEgens for Biomedical Applications

“…The recently emerging second NIR (NIR-II, 1000–1700 nm) window exhibits great promise for bioapplications as it possesses significantly reduced light–tissue interaction and enables large-depth and high-resolution imaging in a living body [ 122 , 123 , 124 , 125 , 126 ]. Zhao and Wu et al reported on a H 2 O 2 -activatable AIE nanoprobe for sensitive disease diagnosis via NIR-II fluorescence and PA imaging [ 127 ]. As displayed in Figure 7 , the low-bandgap D-A compound consisted of two TPE groups that would result in AIE feature and increased conjugation, and two nitrophenyloxoacetamide moieties that could be cleaved in the presence of H 2 O 2 .…”

AIE-active luminogens as highly efficient free-radical ROS photogenerator for image-guided photodynamic therapy

“…The strongly electron-donating carbazole unit and p-bridge of the thiophene group can realize strong intramolecular charge transfer (ICT) for red-shied emission in the NIR region, thus reducing the interference from background biological uorescence for precise imaging. [31][32][33][34] The hydrophilic pyridinium salt group can maintain good miscibility of TCM-CPS in biological media, thus achieving desirable "off-on" uorescence. Given that the pyridinium salt group and three cyano groups are very strong electron-withdrawing groups, the strong donor-p-acceptor (Dp-A) character of TCM-CPS can greatly separate the HOMO-LUMO distribution to decrease DE ST , thereby enhancing the intersystem crossing process (ISC) for higher ROS generation.…”

A nitrobenzoxadiazole-based near-infrared fluorescent probe for the specific imaging of H2S in inflammatory and tumor mice

“…Compared with these methods, fluorescent probes are extremely attractive because of their simple operation, high sensitivity, non-destructive analysis, and good compatibility with biological samples. 21–28 So far, various fluorescent probes for detecting H 2 S have been developed based on different fluorophores, such as rhodamine, 29 coumarin, 30 1,8-naphthalimide 31 and BODIPY. 32 However, the application of these probes in vivo is unsatisfactory because they have short emission wavelengths (<600 nm), resulting in high background signals and low tissue penetration.…”