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.

Lanthanide based upconversion (UC) nanoprobes have emerged as promising agents for biological applications. Extending the excitation light to the second near‐infrared (NIR‐II), instead of the traditional 980/808 nm light, and realizing NIR‐II responsive single‐band red UC emission is highly demanded for bioimaging application, which has not yet been explored. Here, a new type of NIR‐II (1532 nm) light responsive UC nanoparticles (UCNPs) with enhanced single‐band red UC emission and controllable phase and size is designed by introducing Er3+ as sensitizer and utilizing Mn2+ as energy manipulator. Through tuning the content of Mn2+ in NaLnF4:Er/Mn, the crystal phase, size, and emitting color are readily controlled, and the red‐to‐green (R/G) ratio is significantly increased from ≈20 to ≈300, leading to NIR‐II responsive single band red emission via efficient energy transfer between Er3+ and Mn2+. In addition, the single band red emitting intensity can be further improved by coating shell to avoid the surface quenching effect. More importantly, NIR‐II light activated red UC bioimaging and photodynamic therapy through loading photosensitizer of zinc phthalocyanine are successfully achieved for the first time. These findings provide a new strategy of designing NIR‐II light responsive single‐band red emissive UCNPs for biomedical applications.

An endogenous H 2 S-triggered intelligent optical nanoprobe combining second near-infrared (NIR-II) fluorescence with photoacoustic (PA) imaging can provide more comprehensive information to further improve the sensitivity and reliability of diagnosis for colorectal tumor, which is rarely explored. Herein, an endogenous H 2 S-triggered SiO 2 @Ag nanoprobe was designed for in situ dual-modal NIR-II/PA imaging of colorectal cancer. The designed dual-modal nanoprobe can be converted to SiO 2 @Ag 2 S after in situ biosynthesis via a sulfuration reaction with the overexpressed endogenous H 2 S in the colorectal tumor. More importantly, the designed SiO 2 @Ag nanoprobe exhibits high sensitivity and specificity for diagnosing colorectal cancer in vivo via dual-modal NIR-II/PA imaging. These results provide a new NIR-II/PA dual-modal imaging strategy for noninvasive intelligent detection of colorectal cancer.

Excessive production of hydrogen sulfide (H2S) plays a crucial role in the progress of colon cancer. Construction of tumor‐specific H2S‐activated smart nanoplatform with controllable biodegradation is of great significance for precise and sustainable treatment of colon cancer. Herein, an endogenous H2S triggered Co‐doped polyoxometalate (POM‐Co) cluster with self‐adjustable size, controlled biodegradation, and sustainable cyclic depletion of H2S/glutathione (GSH) is designed for synergistic enhanced tumor‐specific photothermal and chemodynamic therapy. The designed POM‐Co nanocluster holds H2S responsive “turn‐on” photothermal property in colon cancer via self‐assembling to form large‐sized POM‐CoS, enhancing the accumulation at tumor sites. Furthermore, the formed POM‐CoS can gradually biodegrade, resulting in release of Co2+ and Mo6+ for Co(II)‐catalyzed •OH production and Russell mechanism‐enabled 1O2 generation with GSH consumption, respectively. More importantly, the degraded POM‐CoS is reactivated by endogenous H2S for recyclable and sustainable consumption of H2S and GSH, resulting in tumor‐specific photothermal/chemodynamic continuous therapy. Therefore, this study provides an opportunity of designing tumor microenvironment‐driven nanoprobes with controllable biodegradation for precise and sustainable anti‐tumor therapy.

There are tricky challenges in tumor therapy due to the hypoxic tumor microenvironment, inevitably inhibiting the treatment efficacy of the traditional photodynamic therapy (PDT), radiation therapy (RT), and sonodynamic therapy (SDT). Herein, to overcome tumor hypoxia limitation, we constructed a near-infrared II (NIR-II) light-triggered thermodynamic therapy (TDT) nanoplatform of Au@ mSiO 2 -AIPH@PCM/PEG (ASAPP) by integrating the Au nanorods (Au NRs) and thermally activated alkyl free radical-releasing molecules (AIPH). Au NRs@mSiO 2 was used as a photothermally responsive material and AIPH carrier, and the hot-melt phase-change material (PCM) was used as a capping agent to prevent leakage of AIPH during blood circulation. Upon NIR-II light irradiation, heat-triggered free radical release from AIPH was successfully achieved for killing cancer cells in vitro and in vivo without oxygen dependence, leading to synergistically enhanced antitumor therapy.