Metformin as a hypoglycemic drug for antidiabetic treatment has emerged as a multipotential drug for many disease treatments such as cognitive disorders, cancers, promoting weight loss. However, overdose uptake may upregulate the hepatic H 2 S level, subsequently leading to serious liver injury and toxicity. Therefore, developing intelligent second near-infrared (NIR-II) emitting nanoprobes by using endogenous H 2 S as a smart trigger for noninvasive highly specific in situ monitoring of the metformin-induced hepatotoxicity is highly desirable, which is rarely explored. Herein, an endogenous H 2 S activated orthogonal NIR-II emitting myrica rubra-like nanoprobe based on NaYF 4 :Gd/ Yb/Er@NaYF 4 :Yb@SiO 2 coated with Ag nanodots was explored for highly specific in vivo ratiometrically monitoring of hepatotoxicity. The designed nanoprobes were mainly uptaken by the liver and subsequently converted to NaYF 4 :Gd/Yb/Er@NaYF 4 :Yb@SiO 2 @Ag 2 S via in situ sulfuration reaction triggered by the overexpressed endogenous H 2 S in the injured liver tissues, finally leading to a turn-on orthogonal emission centered at 1053 nm (irradiation by 808 nm laser) and 1525 nm (irradiation by 980 nm laser). The designed nanoprobe presents a high detection limit down to 0.7 nM of H 2 S. More importantly, the in situ highly specific ratiometric imaging of the metformininduced hepatotoxicity was successfully achieved by using the activatable orthogonal NIR-II emitting probe. Our results provide an NIR-II ratiometric fluorescence imaging strategy for highly sensitive/specific diagnosis of hepatotoxicity levels induced by metformin.
Overexpression of endogenous H 2 S is one of the key characteristic in colon cancer. However, developing endogenous H 2 S-activated optical probes for specific diagnosis of colorectal cancer is rarely explored. Herein, an in situ H 2 S-activatable second near-infrared (NIR-II)-emitting nanoprobe based on Ag-chicken egg white (Ag-CEW) complex for intelligently lighting up colorectal cancer was explored. The designed Ag-CEW complex holds efficient NIR-II emission of 1,000-1,400 nm via endogenous H 2 S-induced in situ chemical reaction to form Ag 2 S quantum dots (QDs). After reaction, the designed Ag-CEW complex with high photo-stability and biocompatibility was successfully used for NIR-II imaging-guided specific visualization and precise location of colorectal cancer via endogenous H 2 S activation. Therefore, our findings provide a new route for specifically targeting diagnosis of colon cancer based on the in situ-activatable NIR-II probe.
Gas‐based therapy has emerged as a new green therapy strategy for anti‐tumor treatment. However, the therapeutic efficacy is still restricted by the deep tissue controlled release, poor lymphocytic infiltration, and inherent immunosuppressive tumor microenvironment (TME). Herein, a new type of nanovaccine is designed by integrating low dose soft X‐ray‐triggered CO releasing lanthanide scintillator nanoparticles (ScNPs: NaLuF4:Gd,Tb@NaLuF4) with photo‐responsive CO releasing moiety (PhotoCORM) for synergistic CO gas/immuno‐therapy of tumors. The designed nanovaccine presents significantly boosted radioluminescence and enables deep tissue CO generation at unprecedented tissue depths of 5 cm under soft X‐ray irradiation. Intriguingly, CO as a superior immunogenic cell death (ICD) inducer further reverses the deep tissue immunosuppressive TME and concurrently activates adaptive anti‐tumor immunity through efficient reactive oxygen species (ROS) generation. More importantly, the designed nanovaccine presents efficient growth inhibition of both local and distant tumors via a soft X‐ray activated systemic anti‐tumor immunoresponse. This work provides a new strategy of designing anti‐tumor nanovaccines for synergistic deep tissue gas‐therapy and remote soft X‐ray photoactivation of the immune response.
Optical bioimaging that works in the second near infrared region (NIR-II, 1000-1700 nm) has emerged as a next generation imaging technique with superior imaging sensitivity and spatial resolution compared to traditional optical imaging utilizing visible and near-infrared lights (below 900 nm). Herein, a new Sc-based NIR-II probe was explored for high performance NIR-II in vivo bioimaging and optical imaging-guided non-invasive brain blood vessel visualization. The lanthanide doped Sc-based probes (KSc2F7:Yb3+/Er3+) possess a pure orthorhombic phase structure with size control by adjusting the F- ion content. These probes present a dominant red upconversion (UC) emission, which is significantly different from the traditional NaYF4:Yb/Er host, which usually has a green UC emission. More importantly, apart from the dominant red UC emission, these probes also possess a strong NIR-II downconversion (DC) emission centered at 1525 nm, which is usually ignored for bioimaging applications. In vivo NIR-II imaging reveals that our explored Sc-based nanorods are promising probes for highly sensitive optical imaging. Moreover, non-invasive through-skull fluorescence bioimaging of brain vessels with high spatial resolution was demonstrated. Therefore, it is expected that Sc-based nanomaterials with unique dominant red UC and DC NIR-II emissions beyond 1500 nm are ideal probes for bio-applications.
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