Activatable Fluorescent-Photoacoustic Integrated Probes with Deep Tissue Penetration for Pathological Diagnosis and Therapeutic Evaluation of Acute Inflammation in Mice.

Inflammation is associated with many diseases, so the development of an excellent near infrared fluorescent (NIRF) and photoacoustic (PA) dual-modality probe is crucial for the accurate diagnosis and efficacy evaluation of inflammation. However, most of the current NIRF/PA scaffolds are based on repurposing existing fluorescent dye platforms that exhibit non-optimal properties for both NIRF and PA signal outputs. Herein, we developed a novel dye scaffold QL-OH by optimizing the NIRF and PA signal of classical hemicyanine dyes. Based on this optimized dye, we developed the first NIRF/PA dual-mode carbon monoxide (CO) probe QL-CO for noninvasive and sensitive visualization of CO levels in deep inflammatory lesions in vivo. The novel probe QL-CO exhibited rapid and sensitive NIRF775/PA730 dual activation responses toward CO. In addition, the CO-activated probe QL-CO was successfully used for the diagnosis of inflammation and evaluation of anti-inflammation drug efficacy in living mice though the NIRF/PA dual-mode imaging technology for the first time. More importantly, the probe QL-CO could accurately locate the deep inflammatory lesion tissues (≈1 cm) in mice and obtain 3D PA diagnostic images with deep penetration depth and spatial resolution. Therefore, the new NIRF/PA dual-mode probe QL-CO has high potential for deep-tissue diagnosis imaging of CO in vivo. These findings may provide a new tool and approach for future research and diagnosis of CO-associated diseases.

Real-Time Visualizing Mitophagy-Specific Viscosity Dynamic by Mitochondria-Anchored Molecular Rotor.

Mitophagy, as an evolutionarily conserved cellular process, plays a crucial role in preserving cellular metabolism and physiology. Various microenvironment alterations assigned to mitophagy including pH, polarity, and deregulated biomarkers are increasingly understood. However, mitophagy-specific viscosity dynamic in live cells remains a mystery and needs to be explored. Here, a water-soluble mitochondria-targetable molecular rotor, ethyl-4-[3,6-bis(1-methyl-4-vinylpyridium iodine)-9 H-carbazol-9-yl)] butanoate (BMVC), was exploited as a fluorescent viscosimeter for imaging viscosity variation during mitophagy. This probe contains two positively charged 1-methyl-4-vinylpyridium components as the rotors, whose rotation will be hindered with the increase of environmental viscosity, resulting in enhancement of fluorescence emission. The results demonstrated that this probe operates well in a mitochondrial microenvironment and displays an off-on fluorescence response to viscosity. By virtue of this probe, new discoveries such as the mitochondrial viscosity will increase during mitophagy are elaborated. The real-time visualization of the mitophagy process under nutrient starvation conditions was also proposed and actualized. We expect this probe would be a robust tool in the pathogenic mechanism research of mitochondrial diseases.

Novel activated NIR-II fluorescence/Ratio photoacoustic probe for dual-modality accurate imaging of palladium ions overload in mouse liver.

Palladium contaminants can pose risks to human health and the natural environment. Once Pd2+ enters the body, it can bind with DNA, proteins, and other macromolecules, disrupting cellular processes and causing serious harm to health. Therefore, it becomes critical to develop simple, highly selective and precise methods for detecting Pd2+in vivo. Here, we have successfully developed the first activated second near-infrared region fluorescence (NIR-II FL) and ratio photoacoustic (PA) probe NYR-1 for dual-modal accurate detection of Pd2+ levels. NYR-1 is capable of rapidly (< 60 s) and sensitively detection of Pd2+ in solution, providing switched on NIR-II FL920 and ratio PA808/PA720 dual-mode signal change. More notably, the probe NYR-1 was successfully used for non-invasive imaging of Pd2+ overload in mouse liver by NIR-II FL/Ratio PA dual-modality imaging technology for the first time. Thus, this work opens up a promising dual-modal detection method for the precise detection of Pd2+ in organisms and in the environment.